Method and apparatus for suprachoroidal administration of therapeutic agent

ABSTRACT

An apparatus for delivering therapeutic agent to an eye comprises a body, a cannula, a hollow needle, and an actuation assembly. The cannula extends distally from the body and is sized and configured to be insertable between a choroid and a sclera of a patient&#39;s eye. The actuation assembly is operable to actuate the needle relative to the cannula to thereby drive a distal portion of the needle along an exit axis that is obliquely oriented relative to the longitudinal axis of the cannula. The cannula may be inserted through a sclerotomy incision to position a distal end of the cannula at a posterior region of the eye, between the choroid and sclera. The needle may be advanced through the choroid to deliver the therapeutic agent adjacent to the potential space between the neurosensory retina and the retinal pigment epithelium layer, adjacent to the area of geographic atrophy.

PRIORITY

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/938,956, entitled “Suprachoroidal Approach,” filed Feb. 12, 2014,the disclosure of which is incorporated by reference herein.

This application also claims priority to U.S. Provisional PatentApplication No. 62/049,056, entitled “Suprachoroidal Injector Design,”filed Sep. 11, 2014, the disclosure of which is incorporated byreference herein.

This application also claims priority to U.S. Provisional PatentApplication No. 62/049,089, entitled “Suprachoroidal Suture MeasurementTemplate,” filed Sep. 11, 2014, the disclosure of which is incorporatedby reference herein.

This application also claims priority to U.S. Provisional PatentApplication No. 62/049,100, entitled “Suprachoroidal Procedure Method,”filed Sep. 11, 2014, the disclosure of which is incorporated byreference herein.

This application also claims priority to U.S. Provisional PatentApplication No. 62/049,128, entitled “Suprachoroidal Manual AdvanceInjector and Third Arm,” filed Sep. 11, 2014, the disclosure of which isincorporated by reference herein.

This application also claims priority to U.S. Provisional Patent App.No. 62/104,295, entitled “Method and Apparatus for SuprachoroidalAdministration of Therapeutic Agent,” filed Jan. 16, 2015, thedisclosure of which is incorporated by reference herein.

JOINT RESEARCH STATEMENT

Subject matter disclosed in this application was developed and theclaimed invention was made by, or on behalf of, one or more parties to ajoint research agreement that was in effect on or before the effectivefiling date of the claimed invention. The claimed invention was made asa result of activities undertaken within the scope of the joint researchagreement. The parties to the joint research agreement include EthiconEndo-Surgery, Inc. and Janssen Research & Development, LLC.

BACKGROUND

The human eye comprises several layers. The white outer layer is thesclera, which surrounds the choroid layer. The retina is interior to thechoroid layer. The sclera contains collagen and elastic fiber, providingprotection to the choroid and retina. The choroid layer includesvasculature providing oxygen and nourishment to the retina. The retinacomprises light sensitive tissue, including rods and cones. The maculais located at the center of the retina at the back of the eye, generallycentered on an axis passing through the centers of the lens and corneaof the eye (i.e., the optic axis). The macula provides central vision,particularly through cone cells.

Macular degeneration is a medical condition that affects the macula,such that people suffering from macular degeneration may experience lostor degraded central vision while retaining some degree of peripheralvision. Macular degeneration may be caused by various factors such asage (also known as “AMD”) and genetics. Macular degeneration may occurin a “dry” (nonexudative) form, where cellular debris known as drusenaccumulates between the retina and the choroid, resulting in an area ofgeographic atrophy. Macular degeneration may also occur in a “wet”(exudative) form, where blood vessels grow up from the choroid behindthe retina. Even though people having macular degeneration may retainsome degree of peripheral vision, the loss of central vision may have asignificant negative impact on the quality of life. Moreover, thequality of the remaining peripheral vision may be degraded and in somecases may disappear as well. It may therefore be desirable to providetreatment for macular degeneration in order to prevent or reverse theloss of vision caused by macular degeneration. In some cases it may bedesirable to provide such treatment in a highly localized fashion, suchas by delivering a therapeutic substance in the subretinal layer (underthe neurosensory layer of the retina and above the retinal pigmentepithelium) directly adjacent to the area of geographic atrophy, nearthe macula. However, since the macula is at the back of the eye andunderneath the delicate layer of the retina, it may be difficult toaccess the macula in a practical fashion.

While a variety of surgical methods and instruments have been made andused to treat an eye, it is believed that no one prior to the inventorshas made or used the invention described in the appended claims.

SUMMARY OF THE INVENTION

A first embodiment of the invention includes an apparatus for deliveringtherapeutic agent to an eye. The apparatus comprises a body, a cannula,a hollow needle, and an actuation assembly. The cannula extends distallyfrom the body. The cannula is sized and configured to be insertablebetween a choroid and a sclera of a patient's eye. The cannula defines alongitudinal axis. The needle is slidable relative to the cannula. Theactuation assembly is operable to actuate the needle relative to thecannula to thereby drive a distal portion of the needle along an exitaxis that is obliquely oriented relative to the longitudinal axis of thecannula.

In some versions of the first embodiment, the actuation assemblyincludes an actuation member that is movable relative to the body toactuate the needle.

In some versions of the first embodiment where the actuation member ismovable relative to the body to actuate the needle, the actuation memberis translatable relative to the body to actuate the needle.

In some versions of the first embodiment where the actuation member ismovable relative to the body to actuate the needle, the actuation memberis rotatable relative to the body to actuate the needle.

In some versions of the first embodiment where the actuation member isrotatable relative to the body to actuate the needle, the actuationassembly includes a threaded member that is associated with theactuation member. The threaded member is configured to engage a threadedbore in the body to actuate the needle when the actuation member isrotated relative to the body.

In some versions of the first embodiment, the needle includes a sharpdistal tip.

In some versions of the first embodiment where the needle includes asharp distal tip, the sharp distal tip of the needle comprises a firstbevel, a second bevel, and a third bevel. The first bevel, second bevel,and third bevel are each oriented obliquely relative to each other.

In some versions of the first embodiment, the exit axis is oriented atan angle between approximately 5° and approximately 30° relative to thelongitudinal axis of the cannula.

In some versions of the first embodiment, the exit axis is oriented atan angle between approximately 7° and approximately 9° relative to thelongitudinal axis of the cannula.

In some versions of the first embodiment, the needle includes a bluntdistal tip.

In some versions of the first embodiment, the cannula includes a beveleddistal end. The beveled distal end has a bevel angle, wherein the bevelangle is between approximately 10° and approximately 30°.

In some versions of the first embodiment, the cannula defines aplurality of lumens extending longitudinally through the length of thecannula. At least one lumen of the plurality of lumens is configured toslidably receive the needle.

In some versions of the first embodiment, the cannula has a bendingstiffness between 0.7×10⁻⁶ Nm² and 11.1×10⁻⁶ Nm².

In some versions of the first embodiment, the cannula has a bendingstiffness between 2.0×10⁻⁶ Nm² and 6.0×10⁻⁶ Nm².

In some versions of the first embodiment, the apparatus further comprisea valve assembly. The valve assembly is operable to provide a fluidcoupling between a fluid source and the needle. The valve assembly isconfigured to translate with the needle relative to the body.

A second embodiment of the invention includes a method for use of asurgical instrument. The surgical instrument comprises a cannula and ahollow needle that is movable relative to the cannula. The methodcomprises performing a sclerotomy by forming an incision in the eye ofthe patient, wherein the incision extends through a sclera layer of theeye to provide access to a suprachoroidal space of the eye. The methodfurther comprises inserting the cannula through the sclerotomy. Themethod further comprises advancing the cannula between the choroid andthe sclera to position the distal end of the cannula at a posteriorregion of the suprachoroidal space. The method further comprisesadvancing the needle relative to the cannula and through the choroid andinto the subretinal space, without perforating the retina. The methodfurther comprises delivering a therapeutic agent into the subretinalspace via the advanced needle.

In some versions of the second embodiment, the method further comprisesdelivering a leading bleb of fluid via the advanced needle beforedelivering the therapeutic agent via the advanced needle.

In some versions of the second embodiment, the method further comprisesattaching a suture loop to an eye of a patent. The act of attaching thesuture loop includes threading a suture through at least a portion ofthe eye (e.g., the sclera) of the patient to form at least one loopdefined by the suture. The act of inserting the cannula comprisespassing the cannula through the suture loop.

A third embodiment of the invention includes a method ofsuprachoroidially administering a therapeutic solution to an eye of apatient. The method comprises threading a suture through at least aportion of the eye (e.g., the sclera) of the patient to form at leastone loop defined by the suture. The method further comprises incising atleast a portion of the eye (e.g., the sclera) to provide access to thechoroid of the eye. The method further comprises guiding a cannulathrough the at least one loop defined by the suture and into an incisioncreated by incising at least a portion of the eye (e.g., the sclera).The method further comprises advancing a needle through the cannula topenetrate through the choroid and administer the therapeutic solution.

In some versions of the third embodiment, the method further comprisesguiding the cannula to an injection site by direct visualization throughthe pupil.

BRIEF DESCRIPTION OF THE DRAWINGS

While the specification concludes with claims which particularly pointout and distinctly claim this technology, it is believed this technologywill be better understood from the following description of certainexamples taken in conjunction with the accompanying drawings, in whichlike reference numerals identify the same elements and in which:

FIG. 1 depicts a perspective view of an exemplary instrument forsuprachoroidal administration of a therapeutic agent;

FIG. 2 depicts another perspective view of the instrument of FIG. 1,with a portion of a body removed;

FIG. 3 depicts a detailed view of the distal end of a cannula of theinstrument of FIG. 1;

FIG. 4 depicts a cross-sectional view of the cannula of FIG. 3, with thecross-section taken along line 4-4 of FIG. 3;

FIG. 5A depicts a detailed perspective view of the distal end of aneedle of the instrument of FIG. 1;

FIG. 5B depicts a detailed elevational view of the distal end of aneedle of the instrument of FIG. 1;

FIG. 5C depicts a detailed perspective view of the distal end of anexemplary alternative needle for use with the instrument of FIG. 1;

FIG. 5D depicts a detailed perspective view of the distal end of anotherexemplary alternative needle for use with the instrument of FIG. 1;

FIG. 5E depicts a detailed perspective view of the distal end of stillanother exemplary alternative needle for use with the instrument of FIG.1;

FIG. 5F depicts a detailed perspective view of the distal end of yetanother exemplary alternative needle for use with the instrument of FIG.1;

FIG. 5G depicts a detailed perspective view of the distal end of yetanother exemplary alternative needle for use with the instrument of FIG.1;

FIG. 5H depicts a detailed perspective view of the distal end of yetanother exemplary alternative needle for use with the instrument of FIG.1;

FIG. 5I depicts a detailed perspective view of the distal end of yetanother exemplary alternative needle for use with the instrument of FIG.1;

FIG. 6 depicts a side elevational view of the instrument of FIG. 1;

FIG. 7 depicts another side elevational view of the instrument of FIG.1, with a locking member removed;

FIG. 8 depicts another side elevational view of the instrument of FIG.1, with an actuation member advanced distally to extend the needledistally from the cannula;

FIG. 9 depicts a perspective view of an exemplary support assembly foruse with the instrument of FIG. 1;

FIG. 10 depicts a cross-sectional view of the support assembly of FIG.9;

FIG. 11 depicts another perspective view of the support assembly of FIG.9, showing various axes of movement;

FIG. 12 depicts another perspective view of the support assembly of FIG.9, with the instrument of FIG. 1 disposed in a cradle of the supportassembly;

FIG. 13 depicts a perspective view of an exemplary suture measurementtemplate for use in an exemplary method for the suprachoroidaladministration of a therapeutic agent;

FIG. 14A depicts a top plan view of an eye of a patient, withsurrounding structures of the eye immobilized and a chandelierinstalled;

FIG. 14B depicts a top plan view of the eye of FIG. 14A, with thetemplate of FIG. 13 disposed on the eye;

FIG. 14C depicts a top plan view of the eye of FIG. 14A, with aplurality of markers disposed on the eye;

FIG. 14D depicts a top plan view of the eye of FIG. 14A, with a sutureloop attached to the eye;

FIG. 14E depicts a top plan view of the eye of FIG. 14A, with asclerotomy being performed;

FIG. 14F depicts a top plan view of the eye of FIG. 14A, with theinstrument of FIG. 1 being inserted through the sclerotomy opening andin between the sclera and choroid of the eye;

FIG. 14G depicts a top plan view of the eye of FIG. 14A, with theinstrument of FIG. 1 under direct visualization at the back of the eye,between the sclera and choroid;

FIG. 14H depicts a top plan view of the eye of FIG. 14A, with the needleof the instrument of FIG. 1 being advanced under direct visualization atthe back of the eye, pressing against the outer surface of the choroidcausing the choroid to ‘tent’;

FIG. 14I depicts a top plan view of the eye of FIG. 14A, with the needledispensing a leading bleb under direct visualization at the back of theeye, the needle between the sclera and choroid, and the leading bleb inthe sub retinal space between the choroid and a retina;

FIG. 14J depicts a top plan view of the eye of FIG. 14A, with the needledispensing a therapeutic agent to the eye at the back of the eye,between the sclera and choroid;

FIG. 15A depicts a cross-sectional view of the eye of FIG. 14A, with thecross-section taken about line 15A-15A of FIG. 14A;

FIG. 15B depicts a cross-sectional view of the eye of FIG. 14A, with thecross-section taken about line 15B-15B of FIG. 14E;

FIG. 15C depicts a cross-sectional view of the eye of FIG. 14A, with thecross-section taken about line 15C-15C of FIG. 14F;

FIG. 15D depicts a cross-sectional view of the eye of FIG. 14A, with thecross-section taken about line 15D-15D of FIG. 14G;

FIG. 15E depicts a cross-sectional view of the eye of FIG. 14A, with thecross-section taken about line 15E-15E of FIG. 14H;

FIG. 15F depicts a cross-sectional view of the eye of FIG. 14A, with thecross-section taken about line 15F-15F of FIG. 14I;

FIG. 15G depicts a cross-sectional view of the eye of FIG. 14A, with thecross-section taken about line 15G-15G of FIG. 14J;

FIG. 16A depicts a detailed perspective view of the eye of FIG. 14A,with a suture being initially threaded through the eye;

FIG. 16B depicts a detailed perspective view of the eye and suture ofFIG. 16A, with the suture being further threaded through the sclera ofthe eye to form a loop;

FIG. 16C depicts a detailed perspective view of the eye and suture ofFIG. 16A, with a two loose ends of the suture being tied together;

FIG. 16D depicts a detailed perspective view of the eye and suture ofFIG. 16A, with a second suture being attached to the suture loop of FIG.16B;

FIG. 16E depicts a detailed perspective view of the eye and suture ofFIG. 16A, with the second suture of FIG. 16D cut and tied to the sutureloop of FIG. 16B;

FIG. 17A depicts a detailed cross-sectional view of the eye of FIG. 14Adepicted in the state shown in FIG. 15E;

FIG. 17B depicts a detailed cross-sectional view of the eye of FIG. 14Adepicted in the state shown in FIG. 15F;

FIG. 17C depicts a detailed cross-sectional view of the eye of FIG. 14Adepicted in the state shown in FIG. 15G;

FIG. 18 depicts a perspective view of an exemplary alternativeinstrument for suprachoroidal administration of a therapeutic agent;

FIG. 19 depicts another perspective view of the instrument of FIG. 18,with a portion of a body removed;

FIG. 20 depicts another perspective view of the instrument of FIG. 18,with an actuation member being actuated;

FIG. 21 depicts a perspective view of the distal end of a cannula of theinstrument of FIG. 18, with a needle actuated relative to the cannula;

FIG. 22 depicts a perspective view of the distal end of an exemplaryalternative cannula for use with the instrument of FIG. 1;

FIG. 23 depicts a perspective view of the distal end of a needle of thecannula of FIG. 22;

FIG. 24 depicts a perspective view of the distal end of anotherexemplary alternative cannula for use with the instrument of FIG. 1;

FIG. 25 depicts a perspective view of the distal end of a needle of thecannula of FIG. 24;

FIG. 26 depicts a perspective view of the distal end of an anotherexemplary alternative cannula for use with the instrument of FIG. 1;

FIG. 27 depicts a cross-sectional view of the cannula of FIG. 26, withthe cross-section taken along line 27-27 of FIG. 26;

FIG. 28 depicts a perspective view of the distal end of an exemplaryalternative cannula for use with the instrument of FIG. 1;

FIG. 29 depicts a cross-sectional view of the cannula of FIG. 28, withthe cross-section taken along line 29-29 of FIG. 28;

FIG. 30 depicts a perspective view of the distal end of an exemplaryalternative cannula for use with the instrument of FIG. 1;

FIG. 31A depicts a cross-sectional view of the cannula of FIG. 30, withthe cross-section taken along line 31-31 of FIG. 30;

FIG. 31B depicts a cross-sectional view of an exemplary alternativecannula for use with the instrument of FIG. 1;

FIG. 31C depicts a cross-sectional view of another exemplary alternativecannula for use with the instrument of FIG. 1;

FIG. 31D depicts a cross-sectional view of still another exemplaryalternative cannula for use with the instrument of FIG. 1;

FIG. 32 depicts a perspective view of an exemplary alternative suturemeasurement template for use in a method for the suprachoroidaladministration of a therapeutic agent;

FIG. 33 depicts a perspective view of another exemplary alternativesuture measurement template for use in a method for the suprachoroidaladministration of a therapeutic agent;

FIG. 34 depicts a perspective view of another exemplary alternativeinstrument for suprachoroidal administration of a therapeutic agent;

FIG. 35 depicts a perspective cross-sectional view of the instrument ofFIG. 34, with the cross-section taken along line 35-35 of FIG. 34;

FIG. 36 depicts another perspective cross-sectional view of theinstrument of FIG. 34, with the cross-section taken along line 36-36 ofFIG. 34;

FIG. 37 depicts a cross-sectional view of a body of the instrument ofFIG. 34, with the cross-section taken along line 35-35 if FIG. 34;

FIG. 38 depicts an exploded perspective view of drive assemblycomponents of the instrument of FIG. 34;

FIG. 39 depicts a perspective view of a knob member of the driveassembly of FIG. 38;

FIG. 40 depicts an exploded perspective view of a lead screw member anda nut member of the drive assembly of FIG. 38;

FIG. 41 depicts an exploded perspective view of a clutch assembly of thedrive assembly of FIG. 38;

FIG. 42 depicts an exploded perspective view of a valve assembly of theinstrument of FIG. 34;

FIG. 43 depicts a perspective cross-sectional view of the valve assemblyof FIG. 42;

FIG. 44A depicts a cross-sectional side view of the valve assembly ofFIG. 42, with the valve assembly in first state;

FIG. 44B depicts a cross-sectional side view of the valve assembly ofFIG. 42, with the valve assembly in a second state;

FIG. 44C depicts a cross-sectional side view of the valve assembly ofFIG. 42, with the valve assembly in a third state;

FIG. 45A depicts a partial side cross-sectional view of the instrumentof FIG. 34, with the cross-section taken along line 35-35 of FIG. 34 andthe drive assembly of FIG. 38 in a non-actuated state;

FIG. 45B depicts a partial, cross-sectional side view of the instrumentof FIG. 34, with the cross-section taken along line 35-35 of FIG. 34 andthe drive assembly of FIG. 38 in a first partially actuated state;

FIG. 45C depicts a partial, cross-sectional side view of the instrumentof FIG. 34, with the cross-section taken along line 35-35 of FIG. 34 andthe drive assembly of FIG. 38 in a second partially actuated state;

FIG. 45D depicts a partial, cross-sectional side view of the instrumentof FIG. 34, with the cross-section taken along line 35-35 of FIG. 34 andthe drive assembly of FIG. 38 in a fully actuated state;

FIG. 46A depicts a partial top plan view of proximal components of thedrive assembly of FIG. 38, with the drive assembly in the non-actuatedstate;

FIG. 46B depicts a partial top plan view of proximal components of thedrive assembly of FIG. 38, with the drive assembly in the firstpartially actuated state;

FIG. 46C depicts a partial top plan view of proximal components of thedrive assembly of FIG. 38, with the drive assembly in the secondpartially actuated state;

FIG. 46D depicts a partial top plan view of proximal components of thedrive assembly of FIG. 38, with the drive assembly in the fully actuatedstate;

FIG. 47 depicts a perspective view of an exemplary support assembly foruse with the instrument of FIG. 34;

FIG. 48 depicts a side plan view of the support assembly of FIG. 47; and

FIG. 49 depicts another perspective view of the support assembly of FIG.47.

The drawings are not intended to be limiting in any way, and it iscontemplated that various embodiments of the technology may be carriedout in a variety of other ways, including those not necessarily depictedin the drawings. The accompanying drawings incorporated in and forming apart of the specification illustrate several aspects of the presenttechnology, and together with the description serve to explain theprinciples of the technology; it being understood, however, that thistechnology is not limited to the precise arrangements shown.

DETAILED DESCRIPTION

The following description of certain examples of the technology shouldnot be used to limit its scope. Other examples, features, aspects,embodiments, and advantages of the technology will become apparent tothose skilled in the art from the following description, which is by wayof illustration, one of the best modes contemplated for carrying out thetechnology. As will be realized, the technology described herein iscapable of other different and obvious aspects, all without departingfrom the technology. Accordingly, the drawings and descriptions shouldbe regarded as illustrative in nature and not restrictive.

It is further understood that any one or more of the teachings,expressions, embodiments, examples, etc. described herein may becombined with any one or more of the other teachings, expressions,embodiments, examples, etc. that are described herein. Thefollowing-described teachings, expressions, embodiments, examples, etc.should therefore not be viewed in isolation relative to each other.Various suitable ways in which the teachings herein may be combined willbe readily apparent to those of ordinary skill in the art in view of theteachings herein. Such modifications and variations are intended to beincluded within the scope of the claims.

For clarity of disclosure, the terms “proximal” and “distal” are definedherein relative to a surgeon or other operator grasping a surgicalinstrument having a distal surgical end effector. The term “proximal”refers the position of an element closer to the surgeon or otheroperator and the term “distal” refers to the position of an elementcloser to the surgical end effector of the surgical instrument andfurther away from the surgeon or other operator.

I. Exemplary Instrument with Slider Articulation Feature

FIGS. 1 and 2 show an exemplary instrument (10) that is configured foruse in a procedure for the suprachoroidal administration of atherapeutic agent to an eye of a patient. Instrument (10) comprises aflexible cannula (20), a body (40), and a slidable (60). Cannula (20)extends distally from body (40) and has a generally rectangular crosssection. Cannula (20) is generally configured to support a needle (30)that is slidable within cannula (20), as will be described in greaterdetail below.

In the present example, cannula (20) comprises a flexible material suchas Polyether block amide (PEBA), which may be manufactured under thetrade name PEBAX. Of course, any other suitable material or combinationof materials may be used. Also in the present example, cannula (20) hasa cross-sectional profile dimension of approximately 2.0 mm by 0.8 mm,with a length of approximately 80 mm. Alternatively, any other suitabledimensions may be used.

As will be described in greater detail below, cannula (20) is flexibleenough to conform to specific structures and contours of the patient'seye, yet cannula (20) has sufficient column strength to permitadvancement of cannula (20) between the sclera and choroid of patient'seye without buckling. Several factors may contribute to suitableflexibility of cannula (20). For instance, the durometer of the materialused to construct cannula (20) at least partially characterizes theflexibility of cannula (20). By way of example only, the material thatis used to form cannula (20) may have a shore hardness of approximately27D, approximately 33D, approximately 42D, approximately 46D, or anyother suitable shore hardness. It should be understood that the shorehardness may fall within the range of approximately 27D to approximately46D; or more particularly within the range of approximately 33D toapproximately 46D; or more particularly within the range ofapproximately 40D to approximately 45D. The particular cross-sectionalshape of cannula (20) may also at least partially characterize theflexibility of cannula (20). Additionally, the stiffness of needle (30)disposed within cannula (20) may at least partially characterize theflexibility of cannula (20).

In the present example, the flexibility of cannula (20) may bequantified by calculating a bending stiffness for cannula (20). Bendingstiffness is calculated by the product of the elastic modulus and thearea moment of inertia. By way of example only, one exemplary materialthat may be used to form cannula (20) may have a shore hardness of D27,an elastic modulus (E) of 1.2×10⁷ N/m², and an area moment of inertia(I_(x)) of 5.52×10⁻¹⁴ m⁴, providing a calculated bending stiffness aboutthe x-axis at 0.7×10⁻⁶ Nm². Another exemplary material that may be usedto form cannula (20) may have a shore hardness of D33, an elasticmodulus (E) of 2.1×10⁷ N/m², and an area moment of inertia (I_(x)) of5.52×10⁻¹⁴ m⁴, providing a calculated bending stiffness about the x-axisat 1.2×10⁻⁶ Nm². Another exemplary material that may be used to formcannula (20) may have a shore hardness of D42, an elastic modulus (E) of7.7×10⁷ N/m², and an area moment of inertia (I_(x)) of 5.52×10⁻¹⁴ m⁴,providing a calculated bending stiffness about the x-axis at 4.3×10⁻⁶Nm². Another exemplary material that may be used to form cannula (20)may have a shore hardness of D46, an elastic modulus (E) of 17.0×10⁷N/m², and an area moment of inertia (I_(x)) of 5.52×10⁻¹⁴ m⁴, providinga calculated bending stiffness about the x-axis at 9.4×10⁻⁶ Nm². Thus,by way of example only, the bending stiffness of cannula (20) may fallwithin the range of approximately 0.7×10⁻⁶ Nm² to approximately 9.4×10⁻⁶Nm²; or more particularly within the range of approximately 1.2×10⁻⁶ Nm²to approximately 9.4×10⁻⁶ Nm²; or more particularly within the range ofapproximately 2.0×10⁻⁶ Nm² to approximately 7.5×10⁻⁶ Nm²; or moreparticularly within the range of approximately 2.0×10⁻⁶ Nm² toapproximately 6.0×10⁻⁶ Nm²; or more particularly within the range ofapproximately 3.0×10⁻⁶ Nm² to approximately 5.0×10⁻⁶ Nm²; or moreparticularly within the range of approximately 4.0×10⁻⁶ Nm² toapproximately 5.0×10⁻⁶ Nm².

In the present example, the flexibility of cannula (20) may also bequantified by the following formula:

$\begin{matrix}{\delta = \frac{{FL}^{3\;}}{48\; {EI}}} & (1)\end{matrix}$

In the above equation, bending stiffness (EI) is calculatedexperimentally by deflecting cannula (20) having a fixed span (L) a setdistance to yield a predetermined amount of deflection (δ). The amountof force (F) required for such a deflection may then be recorded. Forinstance, when using such a method cannula (20) may have a span of 0.06m and may be deflected for a given distance. By way of example only, oneexemplary material that may be used to form cannula (20) may require aforce of 0.0188 N to achieve a deflection of 0.0155 m, providing acalculated bending stiffness about the x-axis of 5.5×10⁻⁶ Nm². Inanother exemplary material that may be used to form cannula (20) mayrequire a force of 0.0205 N to achieve a deflection of 0.0135 m,providing a calculated bending stiffness about the x-axis of 6.8×10⁻⁶Nm². In still another exemplary material that may be used to formcannula (20) may require a force of 0.0199 N to achieve a deflection of0.0099 m, providing a calculated bending stiffness about the x-axis of9.1×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0241 N to achieve a deflection of0.0061 m, providing a calculated bending stiffness about the x-axis of1.8×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0190 N to achieve a deflection0.0081 m, providing a calculated bending stiffness about the x-axis of1.0×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0215 N to achieve a deflection of0.0114 m, providing a calculated bending stiffness about the x-axis of8.4×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0193 N to achieve a deflection of0.0170 m, providing a calculated bending stiffness about the x-axis of5.1×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0224 N to achieve a deflection of0.0152 m, providing a calculated bending stiffness about the x-axis of6.6×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0183 N to achieve a deflection of0.0119 m, providing a calculated bending stiffness about the x-axis of6.9×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0233 N to achieve a deflection of0.0147 m, providing a calculated bending stiffness about the x-axis of7.1×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0192 N to achieve a deflection of0.0122, providing a calculated bending stiffness about the x-axis of7.1×10⁻⁶ Nm². In yet another exemplary material that may be used to formcannula (20) may require a force of 0.0201 N to achieve a deflection of0.0201, providing a calculated bending stiffness about the x-axis of4.5×10⁻⁶ Nm². Thus, by way of example only, the bending stiffness ofcannula (20) may fall within the range of approximately 1.0×10⁻⁶ Nm² toapproximately 9.1×10⁻⁶ Nm². It should be understood that in otherexamples, the bending stiffness of cannula may fall within the range ofapproximately 0.7×10⁻⁶ Nm² to approximately 11.1×10⁻⁶ Nm²; or moreparticularly within the range of approximately 2.0×10⁻⁶ Nm² toapproximately 6.0×10⁻⁶ Nm².

Needle (30) may have a bending stiffness that differs from the bendingstiffness of cannula (20). By way of example only, needle (30) may beformed of a nitinol material that has an elastic modulus (E) of 7.9×10¹⁰N/m², and an area moment of inertia (I_(x)) of 2.12×10⁻¹⁷ m⁴, providinga calculated bending stiffness about the x-axis at 1.7×10⁻⁶ Nm². By wayof further example only, the bending stiffness of needle (30) may fallwithin the range of approximately 0.5×10⁻⁶ Nm² to approximately 2.5×10⁻⁶Nm²; or more particularly within the range of approximately 0.75×10⁻⁶Nm² to approximately 2.0×10⁻⁶ Nm²; or more particularly within the rangeof approximately 1.25×10⁻⁶ Nm² to approximately 1.75×10⁻⁶ Nm².

As can be seen in FIGS. 3 and 4, cannula (20) has a generallyrectangular cross-sectional shape. In some examples such a rectangularshape may prevent cannula (20) from rotating as it is inserted into apatient's eye. As will be understood, such a feature may be desirablesuch that needle (30) may exit from cannula (20) in a predictabledirection. In other examples, cannula (20) may have any other suitablecross-sectional shape that may generally prevent rotation as will beapparent to those of ordinary skill in the art in view of the teachingsherein.

Cannula (20) defines three lumens (22, 24) extending longitudinallythrough cannula (20) and terminating at a beveled distal end (26). Inparticular, lumens (22, 24) comprise two side lumens (22) and a singlecentral lumen (24). Side lumens (22) contribute to the flexibility ofcannula (20). Although side lumens (22) are shown as being open atbeveled distal end (26), it should be understood that in some examples,side lumens (22) may optionally be closed at beveled distal end (26). Aswill be described in greater detail below, central lumen (24) isconfigured to receive needle (30) and an optical fiber (34).

Beveled distal end (26) is generally beveled to provide separationbetween the sclera and choroid layers to enable cannula (20) to beadvanced between such layers while not inflicting trauma to the scleraor choroid layers. In the present example, beveled distal end (26) isbeveled at an angle of approximately 15° relative to the longitudinalaxis of cannula (20) in the present example. In other examples, beveleddistal end (26) may have a bevel angle within the range of approximately5° to approximately 50°; or more particularly within the range ofapproximately 5° to approximately 40°; or more particularly within therange of approximately 10° to approximately 30°; or more particularlywithin the range of approximately 10° to approximately 20°.

As described above, needle (30) and optical fiber (34) are disposedwithin central lumen (24). In particular, needle (30) is slidablydisposed within central lumen (24) such that needle (30) may be advanceddistally from beveled distal end (26). Optical fiber (34) of the presentexample is fixedly secured within central lumen (24), although in otherexamples optical fiber (34) may be slidable relative to beveled distalend (26) similar to needle (30).

Both needle (30) and optical fiber (34) pass through a guide member (36)that is disposed within central lumen (24). Guide member (36) isconfigured to direct needle (30) as needle (30) is advanced distallyrelative to beveled distal end (26). In particular, guide member (36) ofthe present example is configured to direct needle (30) along thelongitudinal axis of cannula (20) such that needle (30) is advancedobliquely relative beveled distal end (26). Alternatively, guide member(36) may be configured in other examples to direct needle (30) along apath separate from the longitudinal axis of cannula (20). For instance,guide member (36) of such an example may include a curved channel (notshown) that may impose a curve on needle (30) as it is advanced throughguide member (36). Needle (30) may then be advanced along a path that isoriented at an oblique angle relative to the longitudinal axis ofcannula (20). By way of example only, guide member (36) may urge needle(30) to exit cannula (20) along a path that is oriented at an angle ofapproximately 7° to approximately 9° relative to the longitudinal axisof cannula (20). By way of further example only, guide member (36) mayurge needle (30) to exit cannula (20) along a path that is oriented atan angle within the range of approximately 5° to approximately 30°relative to the longitudinal axis of cannula (20); or more particularlywithin the range of approximately 5° to approximately 20° relative tothe longitudinal axis of cannula (20); or more particularly within therange of approximately 5° to approximately 10° relative to thelongitudinal axis of cannula (20). Although guide member (36) is shownas a separate member relative to cannula (20), it should be understoodthat in other examples guide member (36) may be integral to cannula(20).

Needle (30) of the present example comprises a nitinol hypodermic needlethat is sized to deliver the therapeutic agent while being small enoughto create self sealing wounds as needle (30) penetrates tissuestructures of the patient's eye, as will be described in greater detailbelow. By way of example only, needle (30) may be 35 gauge with a 100 μminner diameter, although other suitable sizes may be used. For instance,the outer diameter of needle (30) may fall within the range of 27 gaugeto 45 gauge; or more particularly within the range of 30 gauge to 42gauge; or more particularly within the range of 32 gauge to 39 gauge. Asanother merely illustrative example, the inner diameter of needle (30)may fall within the range of approximately 50 μm to approximately 200μm; or more particularly within the range of approximately 50 μm toapproximately 150 μm; or more particularly within the range ofapproximately 75 μm to approximately 125 μm.

As can best be seen in FIGS. 5A and 5B, needle (30) has a sharp distalend. Distal end (32) of the present example is a tri-bevelconfiguration. In particular, several bevels (31, 33, 35) converge witheach other to form the distal end. The distal end (32) is formed byfirst grinding or laser cutting a first bevel (31) in needle (30), at anoblique angle relative to the longitudinal axis (LA) of needle (30). Byway of example only, first bevel (31) may be oriented at an angle ofapproximately 30° relative to the longitudinal axis (LA) of needle (30).Next a pair of laterally opposing second bevels (33) are ground or lasercut into needle (30) at an oblique angle relative to the longitudinalaxis (LA) of needle (30). By way of example only, second bevels (33) mayeach be oriented at an angle of approximately 35° relative to thelongitudinal axis (LA) of needle (30).

Finally, a pair of third bevels (35) are ground or laser cut into needle(30) at an oblique angle relative to first bevel (31) and relative toand second bevels (33). Second bevels (33) and third bevels (35) are cutsuch that they are cut into a portion of first bevel (31), while leavingat least a portion of first bevel (31) intact. Bevels (31, 33, 35) allconverge at the distal end of needle to form a sharp tip. Because needle(30) is a hypodermic needle, bevels (31, 33, 35) intersect with anopening (37) in the distal end of needle (30). As can be seen, opening(37) tapers as bevels (31, 33, 35) intersect with opening (37), thusforming an additional cutting edge to further increase the sharpness ofneedle (30). Although needle (30) is shown as having a particular numberand arrangement of bevels (31, 33, 35), in other examples distal end(32) may include any other suitable number of bevels. For instance,distal end (32) may include a single bevel, two bevels, or more thanthree bevels. By way of further example only, distal end (32) mayinclude a bevel formed at an angle that falls within the range ofapproximately 5° and approximately 50°; or more particularly within therange of approximately 15° and approximately 40°; or more particularlywithin the range of approximately 15° and approximately 30°; oralternatively within the range of approximately 25° and approximately35°.

FIGS. 5C-5I show several merely exemplary alternative needles (2730,2830, 2930, 3030, 3130, 3230, 3330, 3430) that may be used withinstrument (10) in place of needle (30). As can be seen in FIG. 5C, onemerely exemplary alternative needle (2730) may be a Touhy needle (2730).Needle (2730) includes a sharp distal end (2732), which is slightlycurved. Needle (2730) further includes an opening (2737) in distal end(2732). Opening (2737) is cut in needle (2730) at an angle to providesharpness to distal end (2732).

FIG. 5D shows another exemplary alternative needle (2830) that may beused with instrument (10) in place of needle (30). Needle (2830) issubstantially the same as needle (30) described above, except needle(2830) is a Franseen needle (2830). As can be seen, needle (2830)comprises a sharp distal tip (2832) having four separate sharp points.Each sharp point is oriented relative to the others in a symmetricalpattern. A parabolic beveled region is disposed between each sharppoint. The beveled regions together with each sharp point define anopening (2837) for fluid delivery.

FIG. 5E shows still another alternative needle (2930) that may be usedwith instrument (10) in place of needle (30). Needle (2930) issubstantially the same as needle (30) described above, except needle(2930) is a Whitacre needle (2830). As can be seen, needle (2930)comprises a sharp conical distal tip (2932) with a lateral opening(2937) disposed proximal to distal tip (2937). Distal tip (2932) may bebeveled at any suitable angle for piercing tissue, similar to bevelangles described above. Opening (2937) may be any suitable distanceproximal to distal tip (2932).

FIG. 5F shows yet another alternative needle (3030) that may be usedwith instrument (10) in place of needle (30). Needle (3030) issubstantially the same as needle (30) described above, except needle(3030) is a Cournand needle (3030). As can be seen, needle (3030)comprises a sharp distal tip (3032) with an opening (3037) defined by abeveled edge. The beveled edge forms two distinct beveled faces—aproximal face and a distal face. Each beveled face has a different bevelangle. For instance, the proximal face is beveled at a generally smallangle relative to the longitudinal axis of needle (3030), while thedistal face is beveled at a generally large angle relative to thelongitudinal axis of needle (3030). It should be understood that thefaces may be beveled at any suitable angle as will be apparent to thoseof ordinary skill in the art in view of the teachings herein.

FIG. 5G shows yet another alternative needle (3130) that may be usedwith instrument (10) in place of needle (30). Needle (3130) issubstantially the same as needle (30) described above, except needle(3130) is a Mengini needle (3130). As can be seen, needle (3130)comprises a sharp distal tip (3132) with an opening (3137) defined by abeveled edge. The beveled edge includes a bevel angle that continuouslyadjusts from one end of the beveled edge to the other. For instance, thebeveled edge initially cuts needle (3130) along a plane that isperpendicular to the longitudinal axis of needle (3130). As the bevelededge extends downwardly, the beveled edge cuts needle (3130) at a planethat is increasingly parallel with the longitudinal axis of needle(3130).

FIG. 5H shows yet another alternative needle (3230) that may be usedwith instrument (10) in place of needle (30). Needle (3230) issubstantially the same as needle (30) described above, except needle(3230) is a back cut bevel needle (3230). As can be seen, needle (3230)comprises a sharp distal tip (3232) with an opening (3237) defined by atop bevel face. Distal tip (3232) also includes two opposing bevel faceson the underside of needle (3230), which intersect with the tip bevelface to thereby form sharp distal tip (3232).

FIG. 5I shows yet another alternative needle (3330) that may be usedwith instrument (10) in place of needle (30). Needle (3330) issubstantially the same as needle (30) described above, except needle(3330) is a Dos Santos needle (3330). As can be seen, needle (3330)comprises a sharp distal tip (3332) with a flat bevel. Needle (3330)further includes two openings (3337) disposed proximal distal tip(3337), which are configured to communicate fluid from needle (3330).The bevel may be beveled at any suitable angle for piercing tissue,similarly to bevel angles described above. Openings (3337) may be anysuitable distance proximally from distal tip (3332) as will be apparentto those of ordinary skill in the art in view of the teachings herein.

Optical fiber (34) of the present example is a single fiber optic strandof fused silica with a polyimide cladding. Although optical fiber (34)is described herein as being a single fiber optic strand, it should beunderstood that in other examples, optical fiber (34) may be comprisedof a plurality of fibers. Moreover, optical fiber (34) may be comprisedof any suitable material such as sapphire or fluoride glasses, plastics,and/or any other suitable material(s). As will be described in greaterdetail below, optical fiber (34) is generally configured to illuminatethe area immediately in front of needle (30) to assist the positioningof needle (30) and/or cannula (20) within the eye of a patient. Itshould be understood that optical fiber (34) is merely optional and inother examples optical fiber (34) may simply be omitted.

Referring back to FIGS. 1-2, body (40) is generally shaped as anelongate rectangle with a curved distal end. The particular shape ofbody (40) that is shown is configured to be grasped by an operator.Alternatively, body (40) may be mounted on a support device or roboticarm for ease of positioning instrument (10), as will be described ingreater detail below.

As can best be seen in FIG. 2, an interior of body (40) includes acannula attachment member (42), a bushing (44), and a needle advancementmember (46). Cannula attachment member (42) fixedly secures a proximalend of cannula (20) to body (40), such that cannula (20) cannot rotateor translate relative to body (40). As described above, needle (30) isslidably disposed within cannula (20). A proximal portion of needle (30)extends through body (40), through bushing (44), and terminates withinadvancement member (46). Bushing (44) is configured to isolate needle(30) from the rest of body (40). In some examples, bushing (44) may bemagnetized to permit selective attachment of busing (44) to a supportdevice or any other ferromagnetic surface.

Needle advancement member (46) comprises a bushing engagement portion(48) and a body engagement portion (50). Bushing engagement portion (48)slidably engages with the proximal end of bushing (44) to locate bushingengagement portion (48) relative to bushing (44). Body engagementportion (50) slidably engages with the inside of body (40) to locateadvancement member (46) relative to body (40). Body engagement portion(50) further extends through the proximal end of body (40) to attach toactuation assembly (60), as will be described in greater detail below.Body (40) and advancement member (46) may further include one or moresets of complementary features that are configured to preventadvancement member (46) from rotating relative to body (40) yet permitadvancement member (46) to translate relative to body (40). Suchcomplementary features may include a key and keyway, pin and slot, hexfeatures, etc.

In the present example, body engagement portion (50) includes a fluidcoupling member (not shown) that is disposed within body engagementportion (50). In particular, bushing engagement portion (48) may behollow or include a lumen such that needle (30) may extend proximallythrough bushing engagement portion (48) to the fluid coupling member ofbody engagement portion (50). As will be described in greater detailbelow, the fluid coupling member of body engagement portion (50) couplesneedle (30) to a supply tube (64) such that supply tube (64) is in fluidcommunication with the lumen of needle (30). Additionally, the fluidcoupling member of body engagement portion (50) couples needle (30) tobody engagement portion (50) such that needle (30) may be advancedthrough body (40) and cannula (20). By way of example only, the fluidcoupling member may comprise a feature that is overmolded about theproximal end of needle, with the feature being secured to bodyengagement portion via threading, interference fitting, welding,adhesive, etc. Various suitable forms that a fluid coupling member maytake will be apparent to those of ordinary skill in the art in view ofthe teachings herein.

Actuation assembly (60) includes an actuation member (62) and a lockingmember (66). Actuation member (62) is secured to the proximal end ofbody engagement portion (50) of advancement member (46). In the presentexample, actuation member (62) is integral with body engagement portion(50) of advancement member (46), although advancement member (46) andbody engagement portion (50) may be coupled by any other suitable means.The shape of actuation member (62) is configured for grasping by anoperator. As will be described in greater detail below, actuation member(62) is configured to translate relative to body (40) to actuateadvancement member (46) within body (40) to thereby advance needle (30)distally through cannula (20). As will also be described in greaterdetail below, actuation member (62) may additionally be rotated relativeto body (40) in some versions.

In the present example, actuation member (62) includes a lumen (notshown) extending longitudinally though actuation member (62). The lumenof actuation member (62) is configured to receive supply tube (64). Inparticular, supply tube (64) connects to the fluid coupling member ofbody engagement portion (50), extends proximally through body engagementportion (50), proximally through actuation member (62), and proximallyout through the proximal end of actuation member (62). Thus, supply tube(64) defines a conduit through actuation member (62) to needle (30) suchthat fluid may be injected via supply tube (64) through needle (30) toan injection site. In the present example, the proximal end of supplytube (64) connects to a fluid source such as a syringe, an automated orsemi-automated injector, or any other suitable fluid source. It shouldbe understood that the proximal end of supply tube (64) may include aluer fitting and/or any other suitable kind of fitting to enable supplytube (64) to be releasably coupled with a fluid source.

Locking member (66) is removably attachable to body engagement portion(50), between body (40) and actuation member (62). As will be describedin greater detail below, locking member (66) fills a space between body(40) and actuation member (62) to prevent actuation member (62) frombeing advanced distally relative to body (40). However, locking member(66) can be removed to selectively permit actuation member (62) to beadvanced distally relative to body (40).

FIGS. 6-8 show an exemplary actuation of instrument (10). In particular,as can be seen in FIG. 6, needle (30) is initially retracted intocannula (20) and locking member (66) is positioned between body (40) andactuation member (62), thereby preventing advancement of actuationmember (62). With instrument (10) in this configuration, cannula (20)may be positioned within an eye of a patient as will be described ingreater detail below.

Once cannula (20) is positioned within an eye of a patient, an operatormay desire to advance needle (30) relative to cannula (20). To advanceneedle (30), an operator may first remove locking member (66) by pullinglocking member (66) away from instrument (10), as can be seen in FIG. 7.Once locking member (66) is removed, actuation member (62) may be movedor translated relative to body (40) to advance needle (30) relative tocannula (20). Actuation member (62) of the present example is onlyconfigured to translate needle (30) and not rotate needle (30). In otherexamples, it may be desirable to rotate needle (30). Accordingly,alternative examples may include features in actuation member (62) torotate and translate needle (30).

In the present example, advancement of actuation member (62) intocontact with body (40) as shown in FIG. 8 corresponds to advancement ofneedle (30) to a position relative to cannula (20) to a predeterminedamount of penetration within an eye of a patient. In other words,instrument (10) is configured such that an operator only has to advanceactuation member (62) into contact with body (40) to properly positionneedle (30) within an eye of a patient. In some examples, thepredetermined amount of advancement of needle (30) relative to cannula(20) is between approximately 0.25 mm to approximately 10 mm; or moreparticularly within the range of approximately 0.1 mm to approximately10 mm; or more particularly within the range of approximately 2 mm toapproximately 6 mm; or more particularly to approximately 4 mm. In otherexamples, contact between actuation member (62) and body (40) may haveno particular significance besides the maximum advancement of needle(30) relative to cannula (20). Instead, instrument (10) may be equippedwith certain tactile feedback features to indicate to an operator whenneedle (30) has been advanced to certain predetermined distancesrelative to cannula (20). Accordingly, an operator may determine thedesired depth of penetration of needle (30) into a patient's eye basedon direct visualization of indicia on instrument and/or based on tactilefeedback from instrument (10). Of course, such tactile feedback featuresmay be combined with the present example, as will be apparent to thoseof ordinary skill in the art in view of the teachings herein.

II. Exemplary Support Assembly

FIGS. 9-12 show an exemplary support assembly (110) that may be used toprovide structural support for instrument (10) described above. Supportassembly (110) is generally configured to provide a selectively movablesupport surface upon which an operator may removably couple instrument(10). Support assembly (110) comprises a flex arm (112) and a rotationassembly (120). Flex arm (112) is comprised of a generally malleablematerial such that an operator may bend flex arm (112) as desired to aposition that may be maintained by flex arm (112) after the bendingforce is removed. By way of example only, flex arm (112) may comprise asolid malleable tube such as a malleable plastic or metal rod. In otherexamples, flex arm (112) may be comprised of a hollow coil of metal orplastic. Of course, flex arm (112) may be comprised of any othersuitable material or may have any other suitable configuration as willbe apparent to those of ordinary skill in the art in view of theteachings herein.

Regardless of the particular construction of flex arm (112), flex arm(112) comprises a bottom end (114) and a top end (116). Although notshown, it should be understood that in some examples bottom end (114)may include a clamp, bracket, or other attachment feature that maypermit support assembly (110) to be attached to a surgical table orother structures used in surgical procedures. By way of example only,bottom end (114) may include one or more features that are configured toselectively secure bottom end (114) to a conventional wrist rest that isused for ophthalmic surgery.

Top end (116) is fixedly secured to rotation assembly (120). As can bestbe seen in FIG. 10, top end (116) of flex arm (112) is fixedly securedto rotation assembly (120) by a threaded stud (118). In particular,threaded stud (118) engages threads cut into the inner diameters of abase (122) of rotation assembly (120) and top end (116) of flex arm(112). In the present example, base (122) is configured to rotaterelative to flex arm (112) and threaded stud (118). Alternatively, base(122) may merely be fastened to flex arm (112) without the capacity torotate relative to flex arm (112). Base (122) is configured to receive aclamping sleeve (124) and tie rod (126). In particular, clamping sleeve(124) is configured to receive tie rod (126) to generally permitclamping sleeve (124) to maintain an orthogonal position relative to topend (116) of flex arm (112), yet also permit clamping sleeve (124) torotate about the longitudinal axis of clamping sleeve (124). As can beseen, clamping sleeve (124) includes a bore (123) that is configured toreceive a spring (125). Spring (125) generates a compressive forcebetween a washer (128) and a bore (not shown) on opposing ends of tierod (126) by forcing clamping sleeve (124) away from base (122), as willbe described in greater detail below.

Rotation assembly (120) further includes a cradle (130) that issupported by a dowel (132). Dowel (132) extends through bores (notshown) in clamping sleeve (124) and tie rod (126). Tie rod (126)together with spring (125) places clamping sleeve (124) and dowel (132)in compression. This compressive force is strong enough to generallymaintain the position of compression sleeve (124) and dowel (132), yetweak enough to permit compression sleeve (124) and/or dowel (132) torotate when acted upon by an operator. Cradle (130) includes anindentation (132) that is configured to receive instrument (10)described above. Additionally, cradle (130) includes a magnet (134)embedded in cradle (130) adjacent to indentation (132). In examples ofinstrument (10) that are equipped with a magnetic bushing similar tobusing (44) described above, magnet (134) may function to removablycouple instrument (10) to cradle (130).

In an exemplary use of support assembly (110), components of supportassembly (110) may be rotated about the axes shown in phantom lines inFIG. 11. In particular, support assembly (110) may be manipulated toorbit cradle (130) about the longitudinal axis of flex arm (112).Likewise, support assembly (110) may be manipulated to orbit cradle(130) about the longitudinal axis of clamping sleeve (124). Finally,support assembly (110) may be manipulated to rotate cradle (130) aboutthe longitudinal axis of dowel (132). The rotatability of components ofsupport assembly (110), along with the malleability of flex arm (112),permit cradle (130) to be moved to a variety of desired positionsrelative to a patient.

In one merely exemplary use, cradle (130) may first be moved into adesired position relative to a patient. Next, instrument (10) may beplaced into cradle (130) as shown in FIG. 12. Alternatively, in anotherexemplary use, instrument (10) may first be placed in cradle (130) andthen cradle (130) may be moved along with instrument (10). Othersuitable ways in which support assembly (110) may be used in combinationwith instrument (10) will be apparent to those of ordinary skill in theart in view of the teachings herein.

III. Exemplary Suture Measurement Template

FIG. 13 shows an exemplary suture measurement template (210) for use ina method for suprachoroidal delivery of a therapeutic agent, as will bedescribed in greater detail below. Generally, template (210) isconfigured to be pressed against an eye of a patient to stamp aparticular pattern of pigment onto the patient's eye. It should beunderstood that reference herein to pressing template (210) against aneye of a patent may include, but is not necessarily limited to, pressingtemplate (210) directly against the sclera (304) surface (e.g., afterthe conjunctiva has been taken down or otherwise displaced). Template(210) comprises a rigid body (220) and a rigid shaft (240). As will bedescribed in greater detail below, body (220) is generally contoured tocorrespond to the curvature of a patient's eye such that body (220) maybe pressed or placed onto at least a portion of the patient's eye. Body(220) comprises an upper guide portion (222) and a plurality ofprotrusions (230) extending distally from an eye face (224) of body(220).

Upper guide portion (222) is generally semi-circular in shape and isdisposed at the top of body (220). The semi-circular shape of upperguide portion (222) has a radius that corresponds to the curvature ofthe limbus of a patient's eye. In other words, upper guide portion (222)curves proximally along a first radius corresponding to a radius ofcurvature of a patient's eyeball; and downwardly (toward thelongitudinal axis of shaft (240)) along a second radius corresponding toa radius of curvature of the limbus of the patient's eye. As will bedescribed in greater detail below, upper guide portion (222) may be usedto properly locate template (210) relative to the limbus of thepatient's eye. Accordingly, any pigmentation that may be deposited ontoa patient's eye by template may be positioned relative to the limbus ofthe patient's eye.

Protrusions (230) are spaced a predetermined distance from upper guideportion (222). In particular, protrusions (230) form a pattern that maycorrespond to relevant marks for use during the method described below.Protrusions (230) of the present example comprise four suture loopprotrusions (230 a-230 h) and two sclerotomy protrusions (230 i, 230 j).Suture loop protrusions (230 a-320 h) and sclerotomy protrusions (230 i,230 j) extend outwardly from body (220) an equal distance such thatprotrusions (230) collectively maintain the curvature defined by body(220). In other words, the tips of protrusions (230 a-230 j) all liealong a curved plane that is defined by a radius of curvaturecomplementing the radius of curvature of the patient's eyeball. The tipsof protrusions (230 a-230 j) are rounded and atraumatic such thatprotrusions (230 a-230 j) may be pressed against the eye withoutdamaging the sclera or other portions of the patient's eye.

Shaft (240) extends proximally from body (220). Shaft (240) isconfigured to permit an operator to grasp template (210) and manipulatebody (220). In the present example, shaft (240) is integral with body(220). In other examples, shaft (240) may be selectively attachable tobody by a mechanical fastening means such as a threaded coupling or amechanical snap fit, etc. In some versions, an operator may be presentedwith a kit comprising a shaft (240) and a plurality of bodies (220). Thebodies (220) may have different curvatures to correspond with differenteyeballs having different radii of curvature. The operator may thusselect an appropriate body (220) from the kit based on the anatomy ofthe particular patient before the operator; and the operator may thensecure the selected body (220) to the shaft (240). Although not shown,it should be understood that the proximal end of shaft (240) mayadditionally include a t-grip, knob, or other gripping feature to permitan operator to more readily grip shaft (240).

In an exemplary use, suture loop protrusions (232) and sclerotomyprotrusions (234) each correspond to a particular portion of the methoddescribed below. In particular, prior to, or during the method describedbelow, an operator may coat protrusions (230) with a biocompatiblepigment or ink by pressing protrusions (230) onto a pigment or ink pad(250), by brushing the pigment or ink onto protrusions (230), or byotherwise applying the pigment or ink to protrusions (230). Onceprotrusions (230) have received the pigment or ink, an operator may markan eye of a patent by pressing protrusions (230) of template (210) ontothe eye of the patient, as will be described in greater detail below.Once template (210) is removed from an eye of a patient, the pigmentfrom protrusions may remain adhered to the eye to mark particular pointsof interest, as will be described in greater detail below.

IV. Exemplary Method for Suprachoroidal Delivery of Therapeutic Agent

FIGS. 14A-17C show an exemplary procedure for suprachoroidal delivery oftherapeutic agent using instrument (10) described above. By way ofexample only, the method described herein may be employed to treatmacular degeneration and/or other ocular conditions. Although theprocedure described herein is discussed in the context of the treatmentof age-related macular degeneration, it should be understood that nosuch limitation is intended or implied. For instance, in some merelyexemplary alternative procedures, the same techniques described hereinmay be used to treat retinitis pigmentosa, diabetic retinopathy, and/orother ocular conditions. Additionally, it should be understood that theprocedure described herein may be used to treat either dry or wetage-related macular degeneration.

As can be seen in FIG. 14A, the procedure begins by an operatorimmobilizing tissue surrounding a patient's eye (301) (e.g., theeyelids) using a speculum (312), and/or any other instrument suitablefor immobilization. While is immobilization described herein withreference to tissue surrounding eye (301), it should be understood thateye (301) itself may remain free to move. Once the tissue surroundingeye (301) has been immobilized, an eye chandelier port (314) is insertedinto eye (301) to provide intraocular illumination when the interior ofeye (301) is viewed through the pupil. In the present example, eyechandelier port (314) is positioned in the inferior medial quadrant suchthat a superior temporal quadrant sclerotomy may be preformed. As can beseen in FIG. 15A, eye chandelier port (314) is positioned to directlight onto the interior of eye (314) to illuminate at least a portion ofthe retina (e.g., including at least a portion of the macula). As willbe understood, such illumination corresponds to an area of eye (301)that is being targeted for delivery of therapeutic agent. In the presentexample, only chandelier port (314) is inserted at this stage, withoutyet inserting an optical fiber (315) into port (314). In some otherversions, an optical fiber (315) may be inserted into chandelier port(314) at this stage. In either case, a microscope may optionally beutilized to visually inspect the eye to confirm proper positioning ofeye chandelier port (314) relative to the target site. In some examples,the target region may be identified by a relative lack of retinalpigmentation. Although FIG. 14A shows a particular positioning of eyechandelier port (314), it should be understood that eye chandelier port(314) may have any other positioning as will be apparent to those ofordinary skill in the art in view of the teachings herein.

Once eye chandelier port (314) has been positioned, the sclera (304) maybe accessed by dissecting the conjunctiva by incising a flap in theconjunctiva and pulling the flap posteriorly. After such a dissection iscompleted, the exposed surface (305) of the sclera (304) may optionallybe blanched using a cautery tool to minimize bleeding. Once conjunctivadissection is complete, the exposed surface (305) of the sclera (304)may optionally be dried using a WECK-CEL or other suitable absorbentdevice. Template (210), described above, may then be used to mark eye(301). As can be seen in FIG. 14B template (210) is positioned to alignwith the limbus of eye (301). An operator may apply a light force totemplate (210) to apply pigment to eye (301). Template (210) is thenremoved, leaving pigment adhered to the exposed surface (305) of thesclera (304) to provide a visual guide (320) for an operator, as can beseen in FIG. 14C. An operator may then use visual guide (320) to attacha suture loop assembly (330) and to perform a sclerotomy. Visual guide(320) comprises a set of suture loop markers (321, 322, 323, 324, 325,326, 327) and a pair of sclerotomy markers (329).

FIG. 14D shows a completed suture loop assembly (330). As will bedescribed in greater detail below, suture loop assembly (330) isgenerally configured to guide cannula (20) of instrument (10) through asclerotomy and into eye (301). FIGS. 16A-16E show an exemplary procedurefor attaching suture loop assembly (330) such as the suture loopassembly (330) that is shown in FIG. 14D. In particular, as can be seenin FIG. 16A, a suture (332) is threaded through eye (301) at a firstsuture loop marker (321), using a curved needle (333). Suture (332) isthen directed out of eye (301) through a second suture loop marker(322). This anchors suture (332) between first suture loop marker (321)and second suture loop marker (322). Suture (332) is then similarlyanchored between third and fourth suture loop markers (323, 324), fifthand sixth suture loop markers (325, 326), and seventh and eighth sutureloop markers (327, 328).

With suture (332) anchored as described above, suture (332) forms theconfiguration shown in FIG. 16B. As can be seen, suture (332) isconfigured to form two loose ends (334), two guide loops (336) and onereturn loop (338). Loose ends (334) may be tied together to permit anoperator to grip loose ends (334), as can be seen in FIG. 16C.Similarly, return loop (338) may be used to attach a second suture (339)to permit an operator to grip return loop (338), as seen in FIGS. 16Dand 16E. It should be understood that loose ends (334) and second suture(339) may be used to assist in stabilizing eye (301) throughout theprocedure. Alternatively, loose ends (334) and second suture (339) maybe simply positioned or tied off away from eye (301). As will bedescribed in greater detail below, guide loops (336) may be used toguide cannula (20) of instrument (10) through the sclerotomy and tothereby help to ensure a tangential entry angle of cannula (20) ascannula (20) enters through the sclerotomy into the suprachoroidalspace, thereby reducing the risk of cannula (20) inflicting trauma onthe choroid (306).

Once suture loop assembly (330) has been attached to eye (301), asclerotomy may be performed on eye (301). As seen in FIG. 14E, eye (301)is cut between sclerotomy markers (329) using a conventional scalpel(313) or other suitable cutting instrument. Although sclerotomy markers(329) are shown as comprising two discrete dots, it should be understoodthat in other examples, markers (329) may comprise any other type ofmarkings such as a solid, dotted or dashed line. The sclerotomyprocedure forms a small incision (316) through sclera (304) of eye(301). As can best be seen in FIG. 15B, the sclerotomy is preformed withparticular care to avoid penetration of the choroid (306). Thus, thesclerotomy procedure provides access to the space between sclera (304)and choroid (306). Once incision (316) is made in eye (301), a bluntdissection may optionally be performed to locally separate sclera (304)from choroid (306). Such a dissection may be performed using a smallblunt elongate instrument, as will be apparent to those of ordinaryskill in the art in view of the teachings herein.

With the sclerotomy procedure performed, an operator may insert cannula(20) of instrument (10) through incision (316) and into the spacebetween sclera (304) and choroid (306). As can be seen in FIG. 14F,cannula (20) is directed through guide loops (336) of suture loopassembly (330) and into incision (316). As described above, guide loops(336) may stabilize cannula (20). Additionally, guide loops (336)maintain cannula (20) in a generally tangential orientation relative toincision (316). Such tangential orientation may reduce trauma as cannula(20) is guided through incision (316) to stabilize cannula (20) and toprevent damage to surrounding tissue. As cannula (20) is inserted intoincision (316) through guide loops (336), an operator may use forceps orother instruments to further guide cannula (20) along an atraumaticpath. Of course, use of forceps or other instruments is merely optional,and may be omitted in some examples. Although not shown, it should beunderstood that in some examples cannula (20) may include one or moremarkers on the surface of cannula (20) to indicate various depths ofinsertion. While merely optional, such markers may be desirable to aidan operator in identifying the proper depth of insertion as cannula (20)is guided along an atraumatic path. For instance, the operator mayvisually observe the position of such markers in relation to guide loops(336) and/or in relation to incision (316) as an indication of the depthto which cannula (20) is inserted in eye (301). By way of example only,one such marker may correspond to an approximately 6 mm depth ofinsertion of cannula (20).

Once cannula (20) is at least partially inserted into eye (301), anoperator may insert an optical fiber (315) into eye chandelier port(314) the fiber (315) had not yet been inserted at this stage. With eyechandelier port (314) in place and assembled with optical fiber (315),an operator may activate eye chandelier port (314) by directing lightthrough optical fiber (315) to provide illumination of eye (301) andthereby visualize the interior of eye (301). Further adjustments to thepositioning of cannula (20) may optionally be made at this point toensure proper positioning relative to the area of geographic atrophy ofretina (308). In some instances, the operator may wish to rotate the eye(301), such as by pulling on sutures (334, 339), to direct the pupil ofthe eye (301) toward the operator in order to optimize visualization ofthe interior of the eye (301) via the pupil.

FIGS. 14G and 15C-15D show cannula (20) as it is guided between sclera(304) and choroid (306) to the delivery site for the therapeutic agent.In the present example, the delivery site corresponds to a generallyposterior region of eye (301) adjacent to an area of geographic atrophyof retina (308). In particular, the delivery site of the present exampleis superior to the macula, in the potential space between theneurosensory retina and the retinal pigment epithelium layer. FIG. 14Gshows eye (301) under direct visualization through a microscope directedthrough the pupil of eye (301), with illumination provided through fiber(315) and port (314). As can be seen, cannula (20) is at least partiallyvisible through a retina (308) and choroid (306) of eye (301). Thus, anoperator may track cannula (20) as it is advanced through eye (301) fromthe position shown in FIG. 15C to the position shown in 15D. Suchtracking may be enhanced in versions where an optical fiber (34) is usedto emit visible light through the distal end of cannula (20).

Once cannula (20) has been advanced to the delivery site as shown inFIG. 15D, an operator may advance needle (30) of instrument (10) asdescribed above with respect to FIGS. 6-8. As can be seen in FIGS.14H-14I, 15E, and 17A, needle (30) is advanced relative to cannula (20)such that needle (30) pierces through choroid (306) without penetratingretina (308). Immediately prior to penetrating choroid (306), needle(30) may appear under direct visualization as “tenting” the surface ofchoroid (306), as can be seen in FIG. 14H. In other words, needle (30)may deform choroid (306) by pushing upwardly on choroid, providing anappearance similar to a tent pole deforming the roof of a tent. Such avisual phenomenon may be used by an operator to identify whether choroid(306) is about to be pierced and the location of any eventual piercing.The particular amount of needle (30) advancement sufficient to initiate“tenting” and subsequent piercing of choroid (306) may be of anysuitable amount as may be determined by a number of factors such as, butnot limited to, general patient anatomy, local patient anatomy, operatorpreference, and/or other factors. As described above, a merely exemplaryrange of needle (30) advancement may be between approximately 0.25 mmand approximately 10 mm; or more particularly between approximately 2 mmand approximately 6 mm.

In the present example, after the operator has confirmed that needle(30) has been properly advanced by visualizing the tenting effectdescribed above, the operator infuses a balanced salt solution (BSS) orother similar solution as needle (30) is advanced relative to cannula(20). Such a BSS solution may form a leading bleb (340) ahead of needle(30) as needle (30) is advanced through choroid (306). Leading bleb(340) may be desirable for two reasons. First, as shown in FIGS. 14I,15F, and 17B, leading bleb (340) may provide a further visual indicatorto an operator to indicate when needle (30) is properly positioned atthe delivery site. Second, leading bleb (340) may provide a barrierbetween needle (30) and retina (308) once needle (30) has penetratedchoroid (306). Such a barrier may push the retinal wall outwardly (as isbest seen in FIGS. 15F and 17B), thereby minimizing the risk of retinalperforation as needle (30) is advanced to the delivery site. In someversions, a foot pedal is actuated in order to drive leading bleb (340)out from needle (30). Alternatively, other suitable features that may beused to drive leading bleb (340) out from needle (30) will be apparentto those of ordinary skill in the art in view of the teachings herein.

Once an operator visualizes leading bleb (340), an operator may ceaseinfusion of BSS, leaving a pocket of fluid as can be seen in FIGS. 14I,15F, and 17B. Next, a therapeutic agent (341) may be infused byactuating a syringe or other fluid delivery device as described abovewith respect to instrument (10). The particular therapeutic agent (341)delivered may be any suitable therapeutic agent configured to treat anocular condition. Some merely exemplary suitable therapeutic agents mayinclude, but are not necessarily limited to, drugs having smaller orlarge molecules, therapeutic cell solutions, certain gene therapysolutions, and/or any other suitable therapeutic agent as will beapparent to those of ordinary skill in the art in view of the teachingsherein. By way of example only, the therapeutic agent (341) may beprovided in accordance with at least some of the teachings of U.S. Pat.No. 7,413,734, entitled “Treatment of Retinitis Pigmentosa with HumanUmbilical Cord Cells,” issued Aug. 19, 2008, the disclosure of which isincorporated by reference herein.

In the present example, the amount of therapeutic agent (341) that isultimately delivered to the delivery site is approximately 50 μL,although any other suitable amount may be delivered. In some versions, afoot pedal is actuated in order to drive agent (341) out from needle(30). Alternatively, other suitable features that may be used to driveagent (341) out from needle (30) will be apparent to those of ordinaryskill in the art in view of the teachings herein. Delivery oftherapeutic agent (341) may be visualized by an expansion of the pocketof fluid (340, 341) as can be seen in FIGS. 14J, 15G, and 17C. As shown,therapeutic agent (341) essentially mixes with the fluid of leading bleb(340) as therapeutic agent (341) is injected into the surprachoroidalspace.

Once delivery is complete, needle (20) may be retracted by slidingactuation assembly (60) proximally relative to body (40); and cannula(30) may then be withdrawn from eye (301). It should be understood thatbecause of the size of needle (20), the site where needle (20)penetrated through choroid (306) is self sealing, such that no furthersteps need be taken to seal the delivery site through choroid (306).Suture loop assembly (330) and chandelier (314) may be removed, andincision (316) in the sclera (304) may be closed using any suitableconventional techniques.

As noted above, the foregoing procedure may be carried out to treat apatient having macular degeneration. In some such instances, thetherapeutic agent (341) that is delivered by needle (20) may comprisecells that are derived from postpartum umbilicus and placenta. As notedabove, and by way of example only, the therapeutic agent (341) may beprovided in accordance with at least some of the teachings of U.S. Pat.No. 7,413,734, entitled “Treatment of Retinitis Pigmentosa with HumanUmbilical Cord Cells,” issued Aug. 19, 2008, the disclosure of which isincorporated by reference herein. Alternatively, needle (20) may be usedto deliver any other suitable substance or substances, in addition to orin lieu of those described in U.S. Pat. No. 7,413,734 and/or elsewhereherein. By way of example only, therapeutic agent (341) may comprisevarious kinds of drugs including but not limited to small molecules,large molecules, cells, and/or gene therapies. It should also beunderstood that macular degeneration is just one merely illustrativeexample of a condition that may be treated through the proceduredescribed herein. Other biological conditions that may be addressedusing the instruments and procedures described herein will be apparentto those of ordinary skill in the art.

V. Exemplary Alternative Instruments and Features

In some examples, it may be desirable to vary certain components orfeatures of the instruments described herein. For instance, it may bedesirable to utilize instruments similar to instrument (10) withalternative mechanisms to actuate needle (30). Yet in other examples, itmay be desirable to utilize instruments similar to instrument (10)equipped with different cannula (20) or needle (30) geometries.Instruments having the above referenced variations may be desirable fordifferent surgical procedures, or surgical procedures similar to theprocedure discussed above, to engage tissue structures of having varyingphysical properties. While certain examples of variations are describedherein, it should be understood that the instruments described hereinmay include any other alternative features as will be apparent to thoseof ordinary skill in the art in view of the teachings herein.

A. Exemplary Alternative Instrument with Rotatable Actuation Feature

FIGS. 18-21 show an exemplary alternative instrument (410) that issimilar to instrument (10) described above. It should be understood thatinstrument (410) may be readily used in place of instrument (10) toperform the medical procedure described above. It should also beunderstood that except as otherwise described herein, instrument (410)of this example is substantially the same as instrument (10) describedabove. Similar to instrument (10), instrument (410) comprises a cannula(420), a body (440), and an actuation assembly (460). Cannula (420) issubstantially the same as cannula (20) described above, such that theparticular details of cannula (420) will not be described further. Body(440) is also substantially the same as body (40) described above,except body (440) is configured with a more compact form factor.Accordingly, further details of body (440) will not be described herein.

The primary difference between instrument (10) and instrument (410) isthat actuation assembly (460) of instrument (410) is rotatable insteadof slidable. As can be seen in FIGS. 18 and 19, actuation assembly (460)includes a rotary actuation member (462), a threaded member (464) and athreaded receiving member (466). Actuation member (462) is generallycylindrical and is configured to be grasped by an operator's fingers.Additionally, in some examples, actuation member (462) may include arubberized surface, knurling, ridges, and/or other features configuredto enhance the gripability of actuation member (462). A fluid supplytube (463) passes through a central bore (not shown) formed throughactuation member (462) and is coupled with the proximal end of needle(430). Thus, fluid supply tube (463) may be used to supply a therapeuticagent and/or other fluids to needle (430). Fluid supply tube (463) isnot secured to actuation member (462) or threaded member (464), suchthat fluid supply tube (463) will not rotate or become twisted whenactuation member (462) and threaded member (464) are rotated.

Threaded member (464) extends distally from actuation member (462) andincludes threading (465) on the exterior of threaded member (464).Threaded member (464) has a length suitable to actuate a needle (430) apredetermined length when threaded member (464) is rotated relative toreceiving member (466) by actuation member (462), as will be describedin greater detail below. The length of threaded member (464) is furthersuitable to extend through threaded receiving member (466) to engage aneedle body (434) on the proximal end of needle (430). Needle body (434)is slidable on a track (412) disposed within body (410). As will bedescribed in greater detail below, needle body (434) together with track(412) generally defines the range of motion of needle (430). Needle body(434) is fixedly secured to the proximal end of needle (430) and isrotatably secured to the distal end of threaded member (464). Thus,needle body (434) translates with threaded member (464) relative to body(440) yet needle body (434) does not rotate with threaded member (464)relative to body (440).

Threaded receiving member (466) is fixedly secured within body (440) andis generally configured to receive threaded member (464). Threadedreceiving member (466) is generally cylindrical with a threaded bore(not shown) extending through threaded receiving member (466). Theexterior of threaded receiving member (466) may include a knurledsurface to maintain the position of threaded receiving member (466)relative to body (440). Of course, knurled surface is merely optionaland in other examples, threaded receiving member (466) may be securedwithin body (440) by mechanical fastening mechanisms, adhesive bonding,and/or other structures or techniques.

The threaded bore of threaded receiving member (466) includes threadingthat is complementary to threading (465) on the exterior of threadedmember (464). Thus, threaded receiving member (466) is configured toreceive threaded member (464) such that threaded member (464) may beadvanced distally or proximally by turning threaded member (464) in agiven direction. In other words, threaded member (464) may serve as atranslating lead screw while threaded receiving member (466) serves as astationary nut.

In an exemplary mode of operation, as can be seen in FIGS. 20 and 21,needle (430) is generally advanced relative to cannula (420) by anoperator rotating actuation member (462). In particular, rotation ofactuation member (462) causes threaded member (464) to correspondinglyrotate. Rotation of threaded member (464) relative to threaded receivingmember (466) causes threaded member (464) to translate relative to body(410) because threaded receiving member (466) is fixed relative to body(410). As threaded member (464) translates, threaded member (464) pushesneedle body (434) distally along track (412). Distal movement of needlebody (434) in turn leads to distal movement of needle (430) relative tobody (410) and cannula (420).

An operator may continue to rotate actuation member (462) until needle(430) has been advanced a desired amount relative to cannula (420).Alternatively, if an operator continues to rotate actuation member (462)indefinitely, further rotation will eventually be prevented by needlebody (434) reaching the distal end of track (412). The operator may thendeliver fluid and/or a therapeutic agent via needle (430). An operatormay then desire to retract needle (430). At such a point an operator maysimply reverse the rotation of actuation member (462). Reversal ofrotation of actuation member (462) causes threaded member (464) totranslate proximally relative to body (410). This in turn causes needlebody (434) to retract proximally relative to body (410); and needle(430) to retract proximally relative to cannula (420). In some versions,instrument (410) includes a resilient member providing a proximal biasto needle (430), thereby further assisting in retraction of needle (430)relative to cannula (420).

B. Exemplary Alternative Cannula

FIGS. 22 and 23 show an exemplary alternative cannula (520) for use withinstruments (10, 410) described above. Cannula (520) is substantiallythe same as cannula (20) described above. For instance, like withcannula (20), cannula (520) is flexible enough to conform to thespecific structures and contours of a patient's eye, yet cannula (520)is rigid enough to permit advancement without buckling. As can be seenin FIG. 22, cannula (520), like cannula (20), comprises three lumens(522, 524) extending longitudinally through cannula (520) andterminating at a beveled distal end (526). Lumens (522, 524) and beveleddistal end (526) are substantially the same as lumens (22, 24) andbeveled distal end (26), described above, such that the particulardetails of these elements will not be described herein.

Cannula (520) of the present example includes a needle (530) and anoptical fiber (534). Optical fiber (534) is substantially the same asoptical fiber (34), described above, such that the particular details ofoptical fiber (534) will not be repeated here. Needle (530) is similarto needle (30) described above, except needle (530) of the presentexample comprises features to enhance the flexibility of needle (530).In particular, as can best be seen in FIG. 23, needle (530) comprises aninner liner (531), a sharp distal end (532), and a series of alternatingslits (533) in the outer surface of needle (530). Inner liner (531)comprises a polyimide or other similar material. Inner liner (531) isgenerally operable to seal needle (530) relative to slits (533).

Sharp distal end (532) is similar to sharp distal end (32) describedabove, except sharp distal end (532) comprises a single bevelconfiguration. In particular, sharp distal end (532) is shown as havinga single 45° bevel relative to the longitudinal axis of needle (530).Like with sharp distal end (32), sharp distal end (532) may be formed bygrinding or laser cutting. It should be understood that although a 45°bevel is shown, any other suitable bevel angle may be used. Forinstance, in some examples the bevel angle may range from 25° to 50°relative to the longitudinal axis of needle.

Slits (533) are arranged in an alternating pattern along the top andbottom of needle (530). In particular, slits (533) are constructed bytransversely laser cutting each slit approximately half way throughneedle (530) from either the top or the bottom of needle (530). Eachslit (533) is in a spaced apart relationship relative to anothersubsequent slit (533). Although a particular spacing is shown, it shouldbe understood that any suitable spacing may be used. For instance, slits(533) of the present example are configured to enhance the flexibilityof needle (530) to permit needle (530) to be bendable away from astraight longitudinal axis of needle (530). Accordingly, in otherexamples, needle (530) may be equipped with a greater number of slits(533) being oriented more closely together to increase the bendabilityof needle (530). Still in other examples, needle (530) may include fewerslits (533) being oriented further apart to increase the stiffness ordecrease the bendability of needle (530). Of course, any other suitableconfiguration of slits (533) may be used as will be apparent to those ofordinary skill in the art in view of the teachings herein. It shouldalso be understood that guide member (36) is omitted from this example,though guide member (36) may instead be included if desired.

FIGS. 24 and 25 show still another alternative cannula (620) for usewith instruments (10, 410) described above. Cannula (620) issubstantially the same as cannula (20) described above. For instance,like with cannula (20), cannula (620) is flexible enough to conform tothe specific structures and contours of a patient's eye, yet cannula(620) is rigid enough to permit advancement without buckling. As can beseen in FIG. 22, cannula (620), like cannula (20), comprises threelumens (622, 624) extending longitudinally through cannula (620) andterminating at a beveled distal end (626). Lumens (622, 624) and beveleddistal end (626) are substantially the same as lumens (22, 24) andbeveled distal end (26), described above, such that the particulardetails of these elements will not be repeated herein.

Cannula (620) of the present example includes a needle (630) and anoptical fiber (634). Optical fiber (634) is substantially the same asoptical fiber (34), described above, such that the particular details ofoptical fiber (634) will not be repeated here. Needle (630) is similarto needle (30) described above, except needle (630) of the presentexample comprises a needle cannula (631) and an inner core wire (633).In particular, as can best be seen in FIG. 25, inner core wire (633) islongitudinally disposed within needle cannula (631). Needle cannula(631) of the present example is an elongate hollow tube comprisingplastic such as polycarbonate, polypropylene, and/or any other suitablematerial(s). The inner diameter of needle cannula (631) is configured toprovide space for inner core wire (633) and to provide additionalclearance for fluid flow. Thus, it should be understood that needlecannula (631) is configured to deliver fluid to the delivery sitedescribed above.

Inner core wire (633) comprises a wire consisting of stainless steel,nitinol, or etc. Inner core wire (633) of the present example has anouter diameter of approximately 1.3 μm, although any other suitablediameter may be used. Inner core wire (633) includes a sharp distal tip(632). Unlike sharp distal tips (32, 532) described above, sharp distaltip (632) of the present example is conical in shape such that sharpdistal tip (632) tapers to a point that is located on the centrallongitudinal axis of inner core wire (633). Sharp distal tip (632) maytaper at any suitable slope as will be apparent to those of ordinaryskill in the art in view of the teachings herein.

In an exemplary use, needle cannula (631) and inner core wire (633) areadvanced simultaneously to pierce tissue. In particular, inner core wire(633) may lead needle cannula (631), with tip (632) being positioneddistally relative to the distal end of needle cannula (631), as bothneedle cannula (631) and inner core wire (633) are advanced relative tocannula (620). Because inner core wire (633) leads needle cannula (631),inner core wire (633) may contact tissue first and begin to penetratevia sharp distal tip (632). As both needle cannula (631) and inner corewire (633) are advanced further, needle cannula (631) may begin topenetrate the tissue through an opening created by sharp distal tip(632). Needle cannula (631) may then deliver fluid through the tissue asdescribed above.

Although needle cannula (631) and inner core wire (633) are describedherein as being advanced simultaneously, it should be understood that inother examples needle cannula (631) and inner core wire (633) may beadvanced separately. For instance, in one merely exemplary mode ofoperation, inner core wire (633) may first be advanced to penetratetissue. Needle cannula (631) may then follow inner core wire (633) aftertissue penetration to deliver fluid. In still other examples, needlecannula (631) may first be advanced to abut tissue. Inner core wire(633) may then be advanced to penetrate the tissue. Finally, needlecannula (631) may be advanced again to penetrate the tissue through anopening created by inner core wire (633). Of course, outer cannula (621)and inner core wire (633) may be used in any other suitable sequence aswill be apparent to those of ordinary skill in the art in view of theteachings herein. It should also be understood that guide member (36) isomitted from this example, though guide member (36) may instead beincluded if desired.

FIGS. 26 and 27 show yet another exemplary alternative cannula (730)that may be used with instruments (10, 410) described above. Cannula(720) is similar to cannula (20) described above. For instance, likewith cannula (20), cannula (720) is flexible enough to conform to thespecific structures and contours of a patient's eye, yet cannula (720)is rigid enough to permit advancement without buckling. However, unlikecannula (20), cannula (720) of the present example includes a bluntdistal end (726) with a central lumen (724) opening therethough. Bluntdistal end (726) may be desirable over other distal ends (26, 526, 626),described herein, to reduce trauma as cannula (720) is advanced withintissue structures of a patient's eye. In particular, blunt distal end(726) is rounded such that cannula (720) includes no corners that maycatch tissue as cannula (720) is advanced through tissue of a patient'seye. Although blunt distal end (726) is shown as having particular radiiof curvature (i.e., along a vertical dimension and along a horizontaldimension), it should be understood that blunt distal end (726) may berounded with any suitable radii as will be apparent to those of ordinaryskill in the art in view of the teachings herein.

As can be seen in FIG. 27, although blunt distal end (726) includes onlycentral lumen (724) opening therethrough, cannula (720) still includesthree lumens (722, 724) similar to cannula (20) described above. Inparticular, two side lumens (722) extend longitudinally though cannula(720) much like side lumens (22) described above. However, unlike sidelumens (22), side lumens (722) are closed at their respective distalends by blunt distal end (726). Central lumen (724) also extendslongitudinally though cannula (720), although as described above centrallumen (724) also extends through blunt distal end (726). Central lumen(724), like central lumen (24) described above, is configured toslidably receive a suitable needle similar to needles (30, 530, 630)described herein.

FIGS. 28 and 29 show an exemplary alternative cannula (820) for use withinstruments (10, 410) described above. Cannula (820) is substantiallythe same as cannula (20) described above. For instance, like withcannula (20), cannula (820) is flexible enough to conform to thespecific structures and contours of a patient's eye, yet cannula (820)is rigid enough to permit advancement without buckling. As can be seenin FIG. 28, cannula (820), like cannula (20), comprises two side lumens(822) and a single central lumen (824) extending longitudinally throughcannula (820) and terminating at a beveled distal end (826). Lumens(822, 824) and beveled distal end (826) are substantially the same aslumens (22, 24) and beveled distal end (26), described above, such thatthe particular details of these elements will not be described herein.To maintain the atraumatic nature of beveled distal end (826), needleguide (880) may be disposed within lumen such that a distal face (882)of needle guide (880) is either flush with beveled distal end (826) orslightly proximal to beveled distal end (826).

Unlike cannula (20), cannula (820) includes a needle guide (880)disposed within central lumen (824) and no optical fiber. Needle guide(880) is generally configured to direct a needle (830) upwardly at anangle relative to the longitudinal axis of cannula (820). In the presentexample, needle guide (880) is comprised of stainless steel, though itshould be understood that any other suitable biocompatible material(s)may be used. The shape of needle guide (880) is configured for insertioninto central lumen (824). In the present example, needle guide (880) issecured within central lumen (824) by a press or interference fit,although in other examples, adhesives, mechanical locking mechanisms,and/or other structures or techniques may be used to secure needle guide(880).

As can best be seen in FIG. 29, needle guide (880) defines an internallumen (882) that is configured to slidably receive needle (830). Inparticular, internal lumen (882) includes a generally straight proximalportion (886) and a curved distal portion (888). Straight proximalportion (886) corresponds to the longitudinal axis of cannula (820),while curved distal portion (888) curves upwardly away from thelongitudinal axis (LA) of cannula (820). Curved distal portion (888) ofthe present example is curved to direct needle (830) along a path thatextends distally from cannula (820) along an exit axis (EA) that is atan angle of approximately 7° to approximately 9° relative to thelongitudinal axis (LA) of cannula (820). It should be understood thatsuch an angle may be desirable to deflect needle (830) in a direction toensure penetration of needle into the choroid (306) and to minimize thepossibility of needle (830) continuing beneath the choroid (306) throughthe suprachoroidal space (as opposed to penetrating through the choroid(306)). It should be further understood that such an angle may bedesirable to deflect needle (830) in a direction to minimize the risk ofneedle (830) perforating the retina after entering the suprachoroidalspace. For instance in some examples, if such an angle is too steep,needle (830) may have a tendency to perforate the retina (308). If theangle is too shallow, needle (830) may fail to penetrate the choroid(306). By way of further example only, curved distal portion (888) mayurge needle (830) to exit cannula (820) along an exit axis (EA) that isoriented at an angle within the range of approximately 5° toapproximately 30° relative to the longitudinal axis (LA) of cannula(820); or more particularly within the range of approximately 5° toapproximately 20° relative to the longitudinal axis (LA) of cannula(820); or more particularly within the range of approximately 5° toapproximately 10° relative to the longitudinal axis (LA) of cannula(820).

In some examples, the desired effect of altering the angle of needle(830) relative to cannula (820) may be achieved without needle guide(880). For instance, in some examples needle (830) may be pre-bent suchthat needle (830) is resiliently biased to a desired angle (e.g., 20°).In such examples, needle (830) may be constrained to follow asubstantially straight path within cannula (820); then advance distallyrelative to cannula (820) in a position that is angled relative tocannula (820). Still in other examples, cannula (820) itself may beconfigured to direct needle (830) at an angle using a curved lumensimilar to curved distal portion (888) of needle guide (880). Yet inother examples the angle of needle (830) may be altered by any othersuitable means as will be apparent to those of ordinary skill in the artin view of the teachings herein.

FIGS. 30 and 31A show an exemplary alternative cannula (2620) for usewith instruments (10, 410) described above. Cannula (2620) issubstantially the same as cannula (20) described above. For instance,like with cannula (20), cannula (2620) is flexible enough to conform tothe specific structures and contours of a patient's eye, yet cannula(2620) is rigid enough to permit advancement without buckling. As can beseen in FIG. 30, cannula (2620), like cannula (20), comprises two sidelumens (2622) and a single central lumen (2624) extending longitudinallythrough cannula (2620) and terminating at a beveled distal end (2626).Lumens (2622, 2624) and beveled distal end (2626) are substantially thesame as lumens (22, 24) and beveled distal end (26), described above,such that the particular details of these elements will not be describedherein. A needle guide (2680) is disposed within lumen (2624) such thatneedle guide (2680) abuts a separate beveled opening (2682) withincannula (2620) that is laterally oriented on the upper surface ofcannula (2620), proximal to beveled distal end (2626).

Unlike cannula (20), cannula (2620) includes a needle guide (2680)disposed within central lumen (2624). Needle guide (2680) is generallyconfigured to direct a needle (2630) upwardly along an exit axis (EA)that is obliquely oriented relative to the longitudinal axis (LA) ofcannula (2620) through beveled opening (2682) of cannula (2620). Needleguide (2680) may be formed of plastic, stainless steel, and/or any othersuitable biocompatible material(s). The shape of needle guide (2680) isconfigured for insertion into central lumen (2624). In the presentexample, needle guide (2680) is secured within central lumen (2624) by apress or interference fit, although in other examples, adhesives and/ormechanical locking mechanisms may be used to secure needle guide (2680).

As can best be seen in FIG. 31A, needle guide (2680) defines an internallumen (2684) that is configured to slidably receive needle (2630). Inparticular, internal lumen (2684) includes a generally straight proximalportion (2686) and a curved distal portion (2688). Straight proximalportion (2686) corresponds to the longitudinal axis (LA) of cannula(2620), while curved distal portion (2688) curves upwardly away from thelongitudinal axis of cannula (2620). Curved distal portion (2688) of thepresent example is curved to direct needle (2630) along an exit axis(EA) that extends distally from cannula (2620) at an angle ofapproximately 7° to approximately 9° relative to the longitudinal axis(LA) of cannula (2620). It should be understood that such an angle maybe desirable to deflect needle (2630) in a direction to ensurepenetration of needle into the choroid (306) and to minimize thepossibility of needle (2630) continuing beneath the choroid (306)through the suprachoroidal space (as opposed to penetrating through thechoroid (306)) and the possibility of retinal perforation. By way offurther example only, curved distal portion (2688) may urge needle(2630) to exit cannula (2620) along an exit axis (EA) that is orientedat an angle within the range of approximately 5° to approximately 30°relative to the longitudinal axis (LA) of cannula (2620); or moreparticularly within the range of approximately 5° to approximately 20°relative to the longitudinal axis (LA) of cannula (2620); or moreparticularly within the range of approximately 5° to approximately 10°relative to the longitudinal axis (LA) of cannula (2620).

Needle (2630) of the present example is substantially the same as needle(30) described above with respect to FIGS. 5A and 5B. In particular,needle (2630) has a sharp distal end (2632). Although not shown, likewith distal end (32) described above, distal end (2632) of the presentexample is a tri-bevel configuration having three separate bevels (notshown) converging with each other to form distal end (2632). Similarly,because needle (2630) is a hypodermic needle, the bevels intersect withan opening (2637) in the distal end of needle (2630). Although needle(2630) is described herein as having three bevels, in other examplesdistal end (32) may include any other suitable number of bevels havingany suitable bevel angle as similarly described above with respect todistal end (2632).

FIGS. 31B-31D show various alternative cannulas (3420, 3520, 3620) thatmay be used in alternative to cannula (2620). Cannulas (3420, 3520,3620) are substantially the same as cannula (2620) described aboveexcept as otherwise noted herein. In particular, like with cannula(2620), each cannula (3420, 3520, 3620) comprises a central lumen (3424,3524, 3624) extending longitudinally through each respective cannula(3420, 3520, 3620) and terminating at a respective distal end (3426,3526, 3626). A needle guide (2680) is disposed within each lumen (3424,3524, 3624) such that needle guide each (3480, 3580, 3680) abuts aseparate beveled opening (3482, 3582, 3682) within each respectivecannula (3420, 3520, 3620) that is laterally oriented on the uppersurface of each cannula (3420, 3520, 3620), proximal to each beveleddistal end (3426, 3526, 3626).

Each needle guide (3480, 3580, 3680) is generally configured to direct arespective needle (3430, 3530, 3630) upwardly along a respective exitaxis (EA) that is obliquely oriented relative to the longitudinal axis(LA) of each cannula (3420, 3520, 3620) through each respective beveledopening (3482, 3582, 3682). Each needle guide (3480, 3580, 3680) definesan internal lumen (3484, 3584, 3684) that is configured to slidablyreceive each respective needle (3430, 3530, 3630). In particular, eachinternal lumen (3484, 3584, 3684) includes a generally straight proximalportion (3486, 3586, 3686) and a curved distal portion (3488, 3588,3688), all of which are similar to proximal portion (2686) and a distalportion (2688) described above.

The general difference between cannulas (3420, 3520, 3620) and cannula(2620) is that each cannula (3420, 3520, 3620) includes an alternativedistal tip (3426, 3526, 3626). For instance, as can be seen in FIG. 31B,cannula (3420) includes a generally rounded distal tip (3426).Similarly, as can be seen in FIG. 31C, cannula (3520) includes a bulbousdistal tip (3526). It should be understood that bulbous distal tip(3526) may be bulbous along a lateral plane (into and out of the pageshowing FIG. 31C) and/or along a vertical plane (along the page showingFIG. 31C). For instance, in some versions, distal tip (3526) is onlybulbous along a lateral plane (into and out of the page showing FIG.31C) and simply looks like rounded distal tip (3526) along a verticalplane (along the page showing FIG. 31C). Finally, as can be seen in FIG.31D, cannula (3620) includes a partially rounded distal tip (3626). Itshould be understood that each distal tip (3426, 3526, 3626) describedherein may provide differing penetration characteristics as each cannula(3420, 3520, 3520) is inserted into an eye of a patient. For instance,rounded or bulbous distal tips (3426, 3526) may provide relatively moreatraumatic characteristics, while partially rounded distal tip (3626)may provide intermediate characteristics with penetrating capabilitiessimilar to distal tip (2626) and atraumatic characteristics similar torounded and bulbous distal tips (3426, 3526). Although certain specificdistal tip (2626, 3426, 3526, 3626) are shown and described herein, itshould be understood that numerous other suitable distal tips may beused as will be apparent to those of ordinary skill in the art in viewof the teachings herein.

C. Exemplary Alternative Suture Measurement Templates

FIG. 32 shows an exemplary alternative suture measurement template (910)that is substantially the same as template (210) described above, exceptas otherwise noted herein. For instance, template (910) comprises a body(920) that is similar to body (220) described above. However, unliketemplate (210), template (910) of the present example lacks a shaft. Aswill be described in greater detail below, body (920) is generallyconfigured to be grasped by forceps in lieu of a shaft. Body (920), likebody (220), comprises an upper guide portion (922). Unlike body (220),body (920) of the present example comprises a plurality of openings(930) such that body (920) may be used like a stencil to mark an eye ofa patient in lieu of using protrusions (230) to mark the eye asdescribed above.

Upper guide portion (922) is generally semi-circular in shape and isdisposed at the top of body (920). The semi-circular shape of upperguide portion (922) has a radius that corresponds to the radius ofcurvature of an limbus of a patient's eye. As will be described ingreater detail below, upper guide portion (922) may be used to positiontemplate (910) relative to the limbus of a patient's eye. Accordingly,any pigmentation that may be deposited onto a patient's eye by usingtemplate (910) may be positioned relative to the limbus of the patient'seye. Openings (930) are similar to protrusions (230) described above inthat openings (930) may be used to mark particular locations of intereston a patient's eye. Openings (930) of the present example comprise foursuture loop openings (932) and a single sclerotomy opening (934).

Unlike body (220), body (920) of the present example includes twograsping members (960). Grasping members (960) extend proximally frombody (920) and are generally configured to be grasped by a forceps orother instrument. Accordingly, an operator may use a forceps or othersurgical instrument to grasp grasping members (960) and manipulate body(920). Although grasping members (960) are shown as elongate rectangles,it should be understood that in other examples any other suitable shapemay be used.

In an exemplary use, suture loop openings (932) and sclerotomy openings(934) each correspond to a particular portion of the method describedabove. In particular, during the method described above, an operator maygrasp one or more grasping members (960) with a forceps or otherinstrument to position body (920) relative to a patient's eye. Once body(920) is positioned, an operator may obtain a pigment pen or otherpigment applying device and use the pen to apply pigment within openings(930). Once pigment has been applied, an operator may remove template(910). Once template (910) is removed from an eye of a patient, thepigment applied through openings (930) may remain adhered to the eye tomark particular points of interest, as was described above.

FIG. 33 shows an exemplary alternative suture measurement template(1010) that is substantially the same as template (210) described above,except as otherwise noted herein. For instance, template (1010)comprises a body (1020) that is similar to body (220) described above.However, unlike template (210), template (1010) of the present examplelacks a shaft. As will be described in greater detail below, body (1020)is generally configured to be grasped by forceps in lieu of a shaft.Body (1020), like body (220), comprises an upper guide portion (1022).Unlike body (220), body (1020) of the present example comprises aplurality of openings (1030) such that body (1020) may be used like astencil to mark an eye of a patient in lieu of using protrusions (230)to mark the eye as described above.

Upper guide portion (1022) is generally semi-circular in shape and isdisposed at the top of body (1020). The semi-circular shape of upperguide portion (1022) has a radius that corresponds to the radius ofcurvature of the limbus of a patient's eye. As will be described ingreater detail below, upper guide portion (1022) may be used to positiontemplate (1010) relative to the limbus of a patient's eye. Accordingly,any pigmentation that may be deposited onto a patient's eye by usingtemplate (1010 may be positioned relative to the limbus of the patient'seye. Openings (1030) are similar to protrusions (230) described above inthat openings (1030) may be used to mark particular locations ofinterest on a patient's eye. Openings (1030) of the present examplecomprise four suture loop openings (1032) and a single sclerotomyopening (1034). In contrast to openings (930) described above, openings(1030) of the present example are enlarged relative to openings (930)such that markings may be more readily made via openings (1030) on aneye of a patient.

Unlike body (220), body (1020) of the present example includes twograsping openings (1060). Grasping openings (1060) are generallyconfigured to be grasped by a forceps or other instrument. Accordingly,an operator may use a forceps or other surgical instrument to graspgrasping openings (1060) and manipulate body (1020). Although graspingopenings (1060) are shown as hexagonal openings, it should be understoodthat in other examples any other suitable shape may be used.

In an exemplary use, suture loop openings (1032) and sclerotomy openings(1034) each correspond to a particular portion of the method describedabove. In particular, during the method described above, an operator maygrasp one or more grasping openings (1060) with a forceps or otherinstrument to position body (1020) relative to a patient's eye. Oncebody (1020) is positioned, an operator may obtain a pigment pen or otherpigment applying device and use the pen to apply pigment within openings(1030). Once pigment has been applied, an operator may remove template(1010). Once template (1010) is removed from an eye of a patient, thepigment applied through openings (1030) may remain adhered to the eye tomark particular points of interest, as was described above.

D. Exemplary Alternative Instrument with Alternative Rotatable ActuationFeature

FIGS. 34-46D show an exemplary alternative instrument (2010) that issimilar to instruments (10, 410) described above. Like with instruments(10, 410), instrument (2010) is generally usable in the proceduredescribed above to deliver a therapeutic fluid suprachoroidally to aneye of a patient. It should therefore be understood that instrument(410) may be readily used in place of instrument (10) to perform themedical procedure described above Like instrument (10), instrument(2010) of this example comprises a cannula (2020), a body (2040), and anactuation assembly (2100). Cannula (2020) includes a Nitinol needle(2030) extending therethrough and is substantially the same as cannula(20) described above. Although cannula (2020) is shown as beingsubstantially similar to cannula (20) described above, it should beunderstood that in any other cannula described herein may be readilyincorporated into instrument (2010). Body (2040) is also similar to body(40) described above, except body (2040) includes a valve actuationrecess (2043) as will be described in greater detail below.

The primary difference between instrument (10) and instrument (2010) isthat actuation assembly (2100) of instrument (2010) is rotatable insteadof being slidable. Additionally, instrument (2010) includes a valveassembly (2200) that operable to change the fluid state of needle(2030). As will be described in greater detail below, actuation assembly(2100) is generally operable to translate valve assembly (2200)longitudinally to thereby translate needle (2030) longitudinallyrelative to cannula (2020) through rotation of a knob member (2110).

As can be seen in FIGS. 35-36 and 38, actuation assembly (2060)comprises knob member (2110), a translation assembly (2130), and aclutch assembly (2160). As best seen in FIG. 39, knob member (2110)comprises an actuation portion (2116) and an elongate driving portion(2118). Additionally, knob member (2110) comprises openings (2111, 2112)on each end defining a lumen (2114) extending longitudinally throughboth actuation portion (2116) and driving portion (2118). Actuationportion (2116) is disposed externally of body (2040) and is generallyconfigured to be gripped and rotated by a hand of an operator to actuateactuation assembly (2060).

Driving portion (2118) of knob member (2110) extends distally into body(2040) and is generally operable to drive various components ofactuation assembly (2100) as will be described in greater detail below.As can best be seen in FIG. 39, driving portion (2118) comprises anannular flange (2120) and two elongate channels (2122). Annular flange(2120) extends radially outwardly from the outer surface of drivingportion (2118). Generally, annular flange (2120) is configured to engagetranslation assembly (2130) as will be described in greater detailbelow. Each channel (2122) of driving portion (2118) is recessed intothe outer surface of driving portion (2118). Channels (2122) havesubstantially similar shapes and include a primary portion (2124) and anassembly portion (2126). Primary portion (2124) extends longitudinallyalong the length of driving portion (2118), terminating proximally ofthe distal end of driving portion (2118) and distally of annual flange(2120). As will be described in greater detail below, primary portion(2124) is configured to slidably engage clutch assembly (2160). Assemblyportion (2126) is L-shaped and intersects with at least a portion ofprimary portion (2124) and the distal end of driving portion (2118). Aswill be understood, assembly portion (2126) is merely included forassembly purposes and generally serves no additional functional purposesafter instrument (2010) has been assembled. Accordingly, it should beunderstood that assembly portion (2126) is merely optional and may beomitted in other examples.

As can best be seen in FIG. 40, translation assembly (2130) comprises athreaded insert (2132) and a translation member (2140). Threaded insert(2132) is generally round with a bore (2134) extending therethrough. Theexterior of threaded insert (2132) includes a pair of outwardlyextending tabs (2136). As can best be seen in FIG. 36, tabs (2136)engage a pair of corresponding recesses (2042) formed within body (2040)to translationally and rotationally secure threaded insert (2132) withinbody (2040). Recess (2042) is also shown in FIG. 37. Referring back toFIG. 40, the interior of threaded insert (2132) includes a pair ofthread members (2138) extending radially inwardly into bore (2134). Aswill be described in greater detail below, thread members (2138)threadingly engage corresponding threading (2148) on the exterior oftranslation member (2140), such that threaded insert (2132) serves as anut. As will be understood, threaded insert (2132) is generally operableto provide translation of translation member (2140) relative to body(2040) when translation member (2140) is rotated relative to threadedinsert (2132).

Translation member (2140) comprises an attachment portion (2142), athreaded portion (2146), and a pair of longitudinally extending arms(2150). Attachment portion (2142) is generally rounded and includes adistal opening (2143) and an attachment channel (2144) in the form of anannular recess. Distal opening (2143) is generally circular and definesa lumen (2145) extending through translation member (2140). Threadedportion (2146) includes threading (2148) that is configured to engagethread members (2138) described above such that translation member(2140) may be translated relative to body (2040) by rotating translationmember (2140) relative to threaded insert (2132). In other words,translation member (2140) serves as a rotating lead screw while threadedinsert (2132) serves as a fixed nut.

Arms (2150) have a generally semicircular profile and extend proximallyfrom threaded portion (2146). Each arm (2150) is separated from theother to define two substantially similar elongate channels (2152)between arms (2150). Each arm (2150) includes an annular channel (2154)disposed near the proximal end of each respective arm (2150). Eachannular channel (2154) corresponds to the other such that togetherannular channels (2154) are configured to receive annular flange (2120)of knob member (2110). It should be understood that arms (2150) arerelatively rigid such that when annular flange (2120) of knob member(2110) is inserted into annular channels (2154), annular flange (2120)is translationally secured therein. Accordingly, when knob member (2110)is coupled to translation member (2140) via arms (2150), knob member(2110) and translation member (2140) may translate unitarily with eachother. However, because of the annular shape of annular channels (2154),knob member (2110) and translation member (2140) may remain free torotate independently of each other.

As can best be seen in FIG. 41, clutch assembly (2160) comprises a firstdrive gear (2162), a second drive gear (2168), a first clutch gear(2172), a second clutch gear (2178), and a spring (2186) disposedbetween each clutch gear (2172, 2178). Each drive gear (2162, 2168) isgenerally circular in shape with a bore (2163, 2169) extendingtherethrough. Each drive gear (2162, 2168) further comprises a pair ofdriving protrusions (2164, 2170) and a plurality of gear teeth (2166,2172). Driving protrusions (2164, 2170) are oriented radially outwardlyand are configured to extend through elongate cannels (2152) defined byarms (2150) of translation member (2140). Driving protrusions (2164,2170) are further configured to be received by corresponding channels(2044, 2046) in body (2040) (see FIGS. 35 and 37) such that drivingprotrusions (2164, 2170) maintain the longitudinal position of drivegears (2162, 2168), yet permit drive gears (2162, 2168) to freely rotaterelative to body (2040) (as seen in FIG. 35). As will be understood,rotation of drive gears (2162, 2168) may cause corresponding rotation oftranslation member (2140) due to driving protrusions (2164, 2170) actingupon arms (2150) of translation member (2140). It should be understoodthat translation member rotates with drive gears (2162, 2168) yettranslates relative to drive gears (2162, 2168).

Gear teeth (2166) of first drive gear (2162) are oriented to protrudeproximally from first drive gear (2162). In contrast, gear teeth (2172)of second drive gear (2168) are oriented to protrude distally fromsecond drive gear (2168). Both sets of gear teeth (2166, 2172) aregenerally saw-tooth shaped and extend circumferentially around theperimeter of the respective faces of each respective drive gear (2162,2168). As will be described in greater detail below, each set of gearteeth (2166, 2172) is configured to mesh with a corresponding set ofgear teeth (2178, 2184) of each corresponding clutch gear (2174, 2180).

Each clutch gear (2174, 2180) is generally circular in shape with a bore(2175, 2181) extending therethrough. Each clutch gear (2174, 2180)further comprises a pair of protrusions (2176, 2182) and a plurality ofgear teeth (2178, 2184). Protrusions (2176, 2182) protrude inwardly intoeach respective bore (2175, 2181). It should be understood thatprotrusions (2176, 2182) are configured to slidibly engage channels(2122) of knob member (2110). As will be described in greater detailbelow, protrusions (2176, 2182) are configured to rotationally secureeach clutch gear (2174, 2180) relative to knob member (2110), whilepermitting each clutch gear (2174, 2180) to translate along the lengthof channels (2127). In other words, clutch gears (2174, 2180) rotatewith knob member (2110) yet translate relative to knob member (2110).

Gear teeth (2178) of first clutch gear (2174) are oriented to protrudedistally from first clutch gear (2174). In contrast, gear teeth (2184)of second clutch gear (2180) are oriented to protrude proximally fromsecond clutch gear (2180). Both sets of gear teeth (2178, 2184) aregenerally saw-tooth shaped and extend circumferentially around theperimeter of the respective faces of each respective clutch gear (2174,2180). As was described above, each set of gear teeth (2178, 2184) isconfigured to mesh with a corresponding set of gear teeth (2166, 2172)of drive gears (2162, 2168).

When each set of gear teeth (2178, 2184) mesh with each respective setof gear teeth (2166, 2172), gear teeth (2178, 2184) are configured todrive or slip relative to gear teeth (2166, 2172) depending on angularrotation in a given direction of each clutch gear (2174, 2180). Forinstance, because of the orientation of gear teeth (2178) of firstclutch gear (2174) relative to the orientation of gear teeth (2166) offirst drive gear (2162), rotation of first clutch gear (2174) in acounter clockwise direction (e.g., when viewed from distally from theproximal end of instrument 2010) will drive rotation of first drive gear(2168). In contrast, rotation of first clutch gear (2174) in a clockwisedirection will result in slippage of first clutch gear (2174) relativeto first drive gear (2168). Similarly, because of the orientation ofgear teeth (2184) of second clutch gear (2180) relative to theorientation of gear teeth (2172) of second drive gear (2168), driving ofsecond drive gear (2168) will occur when second clutch gear (2180) isrotated in the counter clockwise direction; and slippage will occur whensecond clutch gear (2180) is rotated in the clockwise direction.Accordingly, and as will be described in greater detail below, firstclutch gear (2174) is operable to drive first drive gear (2162) whenfirst clutch gear (2174) is rotated in a clockwise direction and secondclutch gear (2180) is operable to drive second drive gear (2168) whensecond clutch gear (2180) is rotated in the clockwise direction.

As can best be seen in FIGS. 42-44B, valve assembly (2200) comprises avalve body (2210), a valve actuator (2230), and a needle coupler (2240).In particular, valve body (2210) comprises a valve housing (2212), acylindrical attachment member (2218) extending proximally from valvehousing (2212), and a coupler insert (2220). Valve housing (2212) isgenerally cylindrical in shape. As can best be seen in FIG. 43, valvehousing (2212) defines a chamber (2214) that is configured to receive apair of supply tubes (2090, 2091) and valve actuator (2230) as will bedescribed in greater detail below. Each side of valve housing (2212)includes a pair of actuator openings (2216), which are configured torotatably receive valve actuator (2230) through valve housing (2212) andinto chamber (2214). In the present example, first supply tube (2090) isconfigured to couple with a source of bleb fluid (340) (e.g., BSS);while second supply tube (2091) is configured to couple with a source oftherapeutic agent (341). It should be understood that each fluid supplytube (2090, 2091) may include a conventional luer feature and/or otherstructures permitting fluid supply tubes (2090, 2091) to be coupled withrespective fluid sources.

The proximal end of valve housing (2212) defines a tube opening (2215)that extends into chamber (2214). As can be seen tube opening (2215) isconfigured to receive a tube (2092) which houses supply tubes (2090,2091). As will be described in greater detail below, tube (2092)surrounds supply tubes (2090, 2091) to prevent inadvertent rotation ofsupply tubes (2090, 2091) by actuation assembly (2100). In the presentexample, tube opening (2215) is sized such that tube (2092) is securedto valve housing (2212) by a compression or interference fit. In otherexamples, tube (2092) may alternatively be secured within tube opening(2215) by adhesive bonding, welding, mechanical fasteners, and/or usingany other suitable structures or techniques.

Attachment member (2218) is configured to couple with the distal end oftranslation member (2140). In particular, attachment member (2218)comprises an cylindrical inwardly directed protrusion (2219) that isconfigured to engage attachment channel (2144) of translation member(2140). It should be understood that in the present example attachmentmember (2218) merely translationally couples valve assembly (2200) totranslation member (2140), while translation member (2140) remains freeto rotate relative to valve assembly (2200). In other words, valveassembly (2200) translates with translation member (2140); yet valveassembly (2200) does not rotate with translation member (2140).

Coupler insert (2220) extends distally from valve housing (2212) and isgenerally configured for insertion into the proximal end of needlecoupler (2240) as will be described in greater detail below. Couplerinsert (2220) is generally cylindrical in shape and comprises an annularrecess (2222) and a distal tip (2224). Annular recess (2222) receives arubber o-ring (2223) or other sealing device. Distal tip (2224) includesa pair of fluid openings (2226) and a conical protrusion (2228). Fluidopenings (2226) open to a pair of tube lumens (2227), which extendthrough coupler insert (2220). As will be described in greater detailbelow, tube lumens (2227) are generally configured to receive supplytubes (2090, 2091) such that fluid may be delivered to needle coupler(2240) via fluid openings (2226). As will also be described in greaterdetail below, conical protrusion (2228) is configured to be received byneedle coupler (2240) to direct fluid from fluid openings (2226) andinto needle (2030).

Valve actuator (2230) comprises a pair of actuation arms (2232), aconnector shaft (2234), and a pinch valve member (2236). Actuator arms(2232) are generally configured to apply a rotational force to connectorshaft (2234) to thereby rotate pinch valve member (2236) about thelongitudinal axis of connector shaft (2234), as will be described below.In the present example, actuation arms (2232) are generally rectangularin shape. In other examples, actuation arms (2232) may be of any othersuitable shape as will be apparent to those of ordinary skill in the artin view of the teachings herein. Connector shaft (2234) is a generallycylindrical shaft that connects each actuation arm (2232) to the other.In the present example, connector shaft (2234) is shown as beingintegral with actuation arm (2232). It should be understood that inother examples, connection shaft (2234) may be a discrete component ofvalve actuator (2230) and may be secured to actuation arms (2232) by anysuitable connection means such as compression fittings, adhesivebonding, welding, mechanical fastening, etc.

Pinch valve member (2236) is generally oblong in shape and includes anannular recess (2238) extending around the perimeter of valve member(2236). Valve member (2236) is shown as being of integral constructionwith connector shaft (2234). It should be understood that, in otherexamples, valve member (2236) may be a discrete component and may beattached to connector shaft (2234) by overmolding, adhesive bonding,welding, etc. Annular recess (2238) has a radius of inner curvature thatcorresponds to the outer diameter of supply tubes (2090, 2091) such thateach supply tube (2090, 2091) may be at least partially disposed withinannular recess (2238). Valve member (2236) is eccentrically positionedon connector shaft (2234). As will be described in greater detail below,the generally oblong shape of valve member (2236) and the eccentricmounting of valve member (2236) permit valve member (2236) to pinch andthereby seal supply tubes (2090, 2091) when valve member (2236) isrotated by connector shaft (2234) via actuation arms (2232).

Needle coupler (2240) comprises a valve body receiving portion (2242)and an elongate needle receiving portion (2250). Valve body receivingportion (2242) is generally cylindrical in shape and defines acorresponding cylindrical chamber (2244). Cylindrical chamber (2244) issized to receive coupler insert (2220) through the proximal end of valvebody receiving portion (2242). At the distal end of chamber (2244),valve body receiving portion (2242) defines a conical recess (2246) thatcorresponds to conical protrusion (2228) of valve body (2210). Thedistal end of conical recess (2246) includes a single fluid opening(2248). As will be described in greater detail below, fluid opening(2248) is in communication with a needle lumen (2254) to communicatefluid to needle (2030). Although conical recess (2246) corresponds toconical protrusion (2228) of valve body (2210), it should be understoodthat conical recess (2246) is sized such that there is a fluid cavity(2249) disposed between conical recess (2246) and conical protrusion(2228). Accordingly and as will be described in greater detail below,fluid may pass from supply tubes (2090, 2091) though fluid openings invalve body (2210), into fluid cavity (2249) and through fluid opening(2248) of conical recess (2246) to needle lumen (2254).

Needle receiving portion (2250) is generally cylindrical in shape andextends distally from valve body receiving portion (2242). The distalend of needle receiving portion (2250) comprises a conical opening(2252) that is configured to receive needle (2030) therethrough. Inparticular, conical opening (2252) is in communication with needle lumen(2254), which extends longitudinally through needle receiving portion(2250). Needle lumen (2254) comprises a distal portion (2256) and aproximal portion (2258). Distal portion (2256) of needle lumen (2254)has a diameter that is large relative to the outer diameter of needle(2030) such that needle (2030) freely disposed within distal portion(2256). Proximal portion (2258) of needle lumen (2254) extendsproximally from distal portion (2256) and intersects with fluid opening(2248) of conical recess (2246). Accordingly, needle (2030) extendsthrough proximal portion (2258) such that needle (2030) is in fluidcommunication with fluid chamber (2249). Proximal portion (2258) isrelatively small in comparison to distal portion (2256). In particular,the diameter of distal portion (2256) is near the outer diameter ofneedle (2030) such that needle (2030) is supported by distal portion(2256). However, it should be understood that the diameter of proximalportion (2258) is large enough to permit needle (2030) to be insertedinto proximal portion (2258).

Proximal portion (2258) further intersects with a lateral notch (2260)in needle receiving portion (2250). Lateral notch (2260) provides accessto proximal portion (2258) from the exterior of needle receiving portion(2250). Although not shown, it should be understood that in someexamples lateral notch (2260) may be filled with an adhesive such asepoxy or similar liquid hardening agents to fixedly secure and sealneedle (2030) within proximal portion of needle lumen (2254).

An exemplary use of valve assembly (2200) can be seen in FIGS. 44A-44C.As can best be seen in FIG. 44A, actuation arms (2232) initially beginin a first state where actuation arms (2232) are oriented rearwardlyalong a plane that is parallel to the longitudinal axis of valveassembly (2200). Valve member (2236) is disposed within chamber (2214)of valve housing (2212) such that supply tubes (2090, 2091) are at leastpartially disposed within annular recess (2238) of valve member (2236).In the first position, first supply tube (2090) is relaxed relative tovalve member (2236) such that valve member (2236) does not pinch orexert a significant amount of force, if any at all, on first supply tube(2090). Thus, leading bleb fluid (340) may be freely communicated toneedle (2030) via first supply tube (2090). However, as can be seen inFIG. 44A, the valve member (2236) is configured and positioned at thisstage such that second supply tube (2091) is pinched or otherwisecompressed by valve member (2236). Thus, with valve assembly (2200) inthe first position one, first supply tube (2090) is open such that fluidmay freely pass through, while second supply tube (2091) is closed suchthat fluid is prevented from flowing through second supply tube (2091).

To actuate valve assembly (2200) to a second state, an operator maygrasp one or both actuation arms (2232) to rotate actuation arms (2232)about the axis of connector shaft (2234). Because of the shape of valveactuation recess (2043) in body (2040), actuation arms (2232) arerotatable distally and upwardly relative to body (2040). Of course, inother examples body (2040) may be configured differently to permitrotation in the opposite direction. As actuation arms (2232) arerotated, valve member (2236) is also rotated by connector shaft (2234).As shown in FIG. 44B, as valve member (2236) reaches an angular positionthat is approximately 90° relative to the position shown in FIG. 44A,the position and configuration of valve member (2236) relative to supplytubes (2090, 2091) allows fluid to flow through both supply tubes (2090,2091). Valve assembly (2200) is thus actuated to a fully opened state byrotating actuation arms (2232) approximately 90°, where actuation arms(2232) are oriented along a plane that is perpendicular to thelongitudinal axis of valve assembly (2200). It should be understoodthat, in some alternative versions, valve assembly (2200) is in a fullyopened state when actuation arms (2232) are oriented along a plane thatis parallel to the longitudinal axis of valve assembly (2200); whilevalve assembly (2200) is in a partially open state when actuation arms(2232) are oriented along a plane that is perpendicular to thelongitudinal axis of valve assembly (2200). Other suitable orientationsand relationships will be apparent to those of ordinary skill in the artin view of the teachings herein. It should also be understood thatinstrument (2010) may be packaged and shipped in the state shown in FIG.44B, preventing supply tubes (2090, 2091) from experiencing the stressof constant pinching before instrument (2010) is used.

After actuation to the second state, actuation arms (2232) may beactuated to a third state shown in FIG. 44C. As can be seen, actuationarms (2232) are oriented forwardly along a plane that is parallel to thelongitudinal axis of valve assembly (2200) when actuation arms (2232)are in the third state. In the third state, second supply tube (2091) isrelaxed relative to valve member (2236) such that valve member (2236)does not pinch or exert a significant amount of force, if any at all, onsecond supply tube (2091). Thus, therapeutic agent (341) may be freelycommunicated to needle (2030) via second supply tube (2091). However, ascan be seen in FIG. 44C, the valve member (2236) is configured andpositioned at this stage such that first supply tube (2090) is pinchedor otherwise compressed by valve member (2236). It should be understoodthat regardless of which particular supply tube (2090) is relaxed orpinched, the configuration in the third position is such that theparticular supply tube (2090, 2091) that was relaxed in the first statewill be pinched in the third state. Similarly, the particular supplytube (2090, 2091) that was pinched in the first state will be relaxed inthe third state. Thus, with valve assembly (2200) in the third state,supply tubes (2090, 2091) are in an opposite state relative to the firststate.

In use, the first state, second state, and third state may be configuredfor different portions of the procedure. For instance, valve assembly(2200) may be initially placed and kept in the first state until theoperator has dispensed the leading bleb of fluid (340) to the targetsite as shown in FIGS. 14I, 15F, and 17B and as described above. Theoperator may then actuate valve assembly (2200) through the second stateto the third state. Upon reaching the third state, the operator maybegin dispensing therapeutic agent (341) to the target site as shown inFIGS. 14J, 15G, and 17C and as described above. It should be understoodthat the operator need not necessarily be dispensing any fluid whilevalve assembly (2200) is at the second state, transitioning to thesecond state, or transitioning from the second state. Other suitableways in which valve assembly (2200) may be used will be apparent tothose of ordinary skill in the art in view of the teachings herein.

FIGS. 45A-45D and 46A-46D illustrate an exemplary use of actuationassembly (2100) to drive valve assembly (2200) longitudinally to therebydrive needle (2030) longitudinally. It should be understood that, wheninstrument (2010) is used in the medical procedure described above, thisactuation of actuation assembly (2100) may be initiated at the stagesshown in FIGS. 14G and 15D to reach the states shown in FIGS. 14H, 15E,and 17A. As can be seen in FIGS. 45A and 46A, actuation assembly (2100),valve assembly (2100), and needle (2030) are initially in a fullyproximal position. In this position, translation member (2140) isdisposed in a proximal position relative to threaded insert (2132) suchthat thread members (2138) engage threading (2148) of translation member(2140) near the distal end of translation member (2140). Because knobmember (2110) is translationally fixed relative to translation member(2140), knob member (2110) is also in a proximal position relative tothreaded insert (2132). As can best be seen in FIG. 46A, channels (2122)are oriented relative to clutch gears (2174, 2180) such that firstclutch gear (2174) is pushed proximally by channels (2122), while secondclutch gear (2180) is pushed proximally by spring (2186) to engagesecond drive gear (2168).

When actuation assembly (2100) is in the proximal position, an operatormay rotate knob member (2110) in either a counter clockwise or clockwisedirection. If knob member (2110) is rotated in the counter clockwisedirection, rotation member (2110) will merely rotate freely. This willoccur for two reasons. First, first clutch gear (2174) is spacedproximally away from engagement with first drive gear (2162) by channels(2122) of knob member (2110). Second, because of the configuration ofgear teeth (2184) of second clutch gear (2180), second clutch gear(2180) will merely slip relative to second drive gear (2168) when secondclutch gear (2180) is rotated counterclockwise by knob member (2110) viachannels (2122) of knob member (2110).

To begin advancement of actuation assembly (2100), valve assembly (2200)and needle (2030), an operator may rotate knob member (2110) in theclockwise direction. As described above, gear teeth (2184) of secondclutch gear (2180) are configured to drive second drive gear (2168) whensecond clutch gear (2180) is rotated in the clockwise direction. Whensecond drive gear (2170) is driven by second clutch gear (2180), drivingprotrusions (2170) of second drive gear (2170) act upon translationmember (2140) to initiate clockwise rotation of translation member(2140) as described above. As translation member (2140) rotatesclockwise, threading (2148) of translation member (2140) act upon threadmembers (2138) of threaded insert (2132). Because threaded insert (2132)is fixed relative to body (2040), threaded insert (2132) acts totranslate translation member (2140) distally as translation member(2140) rotates clockwise. Because translation member (2140) istranslationally fixed relative to knob member (2110), translation member(2140) will act to translate knob member (2110) distally as translationmember (2140) translates distally. Similarly, because valve assembly(2200) is translationally fixed relative to translation member (2140),translation member (2140) will also act to translate valve assembly(2200) distally as translation member (2140) translates.

An operator may continue clockwise rotation of knob member (2110) todrive needle (2030) out of the distal end of cannula (2020). FIGS. 45Cand 46C show actuation assembly (2100), valve assembly (2200), andneedle (2030) in a position immediately prior to actuation assembly(2100), valve assembly (2200), and needle (2030) being translated to afully distal position. In this position, both first clutch gear (2174)and second clutch gear (2180) are in engagement with first drive gear(2164) and second drive gear (2170), respectively. Accordingly, in theposition shown in FIGS. 45C and 46C, knob member (2110) may be rotatedin either the clockwise direction or the counter clockwise direction todrive actuation assembly (2100) distally or proximally, respectively.However, as can best be seen in FIG. 46C, in this position rotationmember (2110) is advanced distally to a position such that furtheradvancement will cause channels (2122) of rotation member (2110) tobegin to drive second clutch gear (2180) out of engagement with seconddrive gear (2170) as will be described in greater detail below.

As can be seen in FIGS. 45D and 46D, rotation member (2110) has beenrotated clockwise direction to translate actuation assembly slightlydistally of the position shown in FIGS. 45C and 46D. In this position,actuation assembly (2100), valve assembly (2200), and needle (2030) areat their furthest distal position relative to body (2040). As can beseen, this position corresponds to needle (2030) being advanced to itsfurthest distal position relative to the distal end of cannula (2020).In the furthest distal position, translation member (2140) is translateddistally such that thread members (2138) of threaded insert (2132)engage threading (2148) of translation member (2140) just distally ofthe proximal end of threading (2148). Because knob member (2110) istranslationally secured relative to translation member (2140),translation member (2140) has translated knob member (2110) to itsfurthest distal position relative to body (2040). When knob member(2110) is in its furthest distal position, channels (2122) of knobmember (2110) are positioned such that channels (2122) drive secondclutch gear (2180) out of engagement with second drive gear (2168).Because first clutch gear (2174) merely slips when rotated in theclockwise direction and second clutch gear (2180) is out of engagementwith second drive gear (2168) at this stage, it should be understoodthat further clockwise rotation of knob member (2110) will merely resultin free rotation of knob member (2110).

With needle (2030) in the distal position, the operator may then actuatevalve assembly (2200) to the open configuration as shown in FIG. 44A toenable the delivery of therapeutic agent via tubes (2090, 2091) andneedle (2030). In other words, at this stage instrument (2010) may beused to perform the steps of the medical procedure shown in FIGS.14I-14J, 15F-15G, and 17B-17C as described above. The operator may thenwish to retract needle (2030).

Although channels (2122) of knob member (2110) drive second clutch gear(2180) out of engagement with second drive gear (2168) when knob member(2110) is in the distal position, it should be understood that firstclutch gear (2180) remains engaged with first drive gear (2162).Accordingly, while further clockwise rotation of knob member (2110) willcause first clutch gear (2180) to slip relative to first drive gear(2162), counter clockwise rotation of knob member (2110) will causefirst clutch gear (2180) to drive first drive gear (2162) in the counterclockwise direction. Rotation of first drive gear (2162) in the counterclockwise direction will rotate translation member (2140) in the counterclockwise direction via driving protrusions (2164) of first drive gear(2162). With translation member (2140) rotated in the counter clockwisedirection, threading (2148) will engage threaded insert (2132) totranslate translation member (2140) proximally. Thus, counter clockwiserotation of rotation member (2110) in the distal position will causetranslation member (2140) to translate proximally thereby retractingactuation assembly (2100), valve assembly (2200), and needle (2030)relative to body (2040).

To return actuation assembly (2100), valve assembly (2200), and needle(2030) to the proximal position shown in FIGS. 45A and 46A, an operatormay continue to rotate rotation member (2110) in the counter clockwisedirection until channels (2122) of rotation member (2110) push firstclutch gear (2174) out of engagement with first drive gear (2162), asdescribed above. Although actuation assembly (2100) is described hereinas generally being used to translate valve assembly (2200) and needle(2030) between the proximal position and the distal position, it shouldbe understood that no such limitation is intended. For instance, anoperator may use actuation assembly (2100) to translate valve assembly(2200) and needle (2030) to any desirable position. In one merelyexemplary use, needle (2030) may only be partially driven distally ofcannula (2020). In another exemplary use, an operator may only partiallyadvance needle (2030) to a point prior to needle advancing out of thedistal end of cannula (2020). An operator may then desire to abort theprocedure or otherwise retract needle (2030) relative to cannula (2020)without ever advancing needle (2030) out of cannula (2020). Of course,any other suitable amount of advancement or retraction may be used aswill be apparent to those of ordinary skill in the art in view of theteachings herein.

It should be understood that as actuation assembly (2100) is rotated toactuate valve assembly (2200) and needle (2030), valve assembly (2200)and needle (2030) remain substantially rotationally stationary relativeto actuation assembly (2100). As described above, such functionality isfacilitated by the coupling between translation member (2140) ofactuation assembly (2100) and valve body (2210) of valve assembly(2200). In addition, it should be understood that tube (2092) extendsthrough lumens (2114, 2145) of rotation member (2110) and translationmember (2140) to prevent rotation member (2110) and translation member(2140) from applying torque to supply tubes (2090, 2091) that mightotherwise cause valve assembly (2200) to rotate. In the present example,it may be desirable to prevent rotation of valve assembly (2200) so thatneedle (2030) translates but does not rotate. This is because of thegeometry of needle (2030) and because of potential interactions of thatgeometry with tissue. Of course, in other examples needle (2030) may beconfigured such that rotation is desired. In such examples, features toprevent rotation of valve assembly (2200) may be omitted or modified aswill be apparent to those of ordinary skill in the art in view of theteachings herein.

E. Exemplary Alternative Support Assembly

FIGS. 47-49 show an exemplary alternative support assembly (2510) thatis similar to support assembly (110) described above. However, unlikesupport assembly (110), support assembly (2510) comprises a relativelyrigid structure and is configured to support instrument (2010) describedabove. Support assembly (2510) comprises a vertical support arm (2520),a clamp assembly (2540), and a lateral support arm (2560). Verticalsupport arm (2520) is relatively rigid and generally permits attachmentof support assembly (2510) to a conventional ophthalmic surgery wristrest or other fixture. Vertical support arm (2520) extends upwardly witha generally rectangular cross-section. An integral cradle member (2522)is included near the upper end of support arm (2520). Cradle member(2522) is generally shaped as a partially cylindrical recess such thatcradle member (2522) is configured to receive a tubular structure thatmay be a part of a wrist rest or other fixture. The upper end of supportarm (2520) further includes a distally extending protrusion (2524) thatis configured to support clamp assembly (2540) as will be described ingreater detail. As will also be described in greater detail below,vertical support arm (2520) may include a bore (not shown) to provideattachment of clamp assembly (2540).

Clamp assembly (2540) comprises an actuation knob (2542) and a clampbracket (2546). Actuation knob (2542) is configured to be rotated by thehand of an operator. A threaded shaft (2544) extends distally fromactuation knob (2542). As will be described in greater detail below,actuation knob (2542) is generally configured to be rotated to engagewith clamp bracket and vertical support arm (2520) via threaded shaft(2544). Clamp bracket (2546) comprises a proximal portion (2548), adistal portion (2552), and a pair of arms (2556) extending betweenproximal portion (2548) and distal portion (2552). Proximal portion(2548) includes an opening (2550) centered in proximal portion (2548).Opening (2550) is configured to receive threaded shaft (2544) ofactuation knob (2542) to permit threaded shaft (2542) to passtherethrough to vertical support arm (2520). Distal portion (2552) isgenerally curved in shape to define a generally partially cylindricalrecess (2554), which complements cradle member (2522) of verticalsupport arm (2520). As will be described in greater detail below, cradlemember (2522) and distal portion (2552) are operable together to clamp atubular structure that may be part of a wrist rest or other fixture.

Arms (2556) extend between proximal portion (2548) and distal portion(2552). In particular, arms (2556) are generally curved upwardly as theyextend between proximal portion (2548) and distal portion (2552). Such acurvature is configured to permit clamping actuation of clamp assembly(2540) as will be described in greater detail below. Each arm (2556)includes a bore (2558) oriented near distal portion (2552). Bore (2558)permits pivotable attachment of arms (2556) to protrusion (2524) ofvertical support arm (2520) via a screw or other fastener.

Lateral support arm (2560) comprises an adjustable collar (2562), aslidable shaft (2568), and an attachment bracket (2572). Adjustablecollar (2562) is generally L-shaped and is configured to selectivelypermit slidable shaft (2568) to slide relative to vertical support arm(2520). In particular, the lower end of adjustable collar (2562)includes an attachment shaft (2564), a distal opening (not shown), aproximal opening (2565), and an adjustment button (2566). Attachmentshaft (2564) extends downwardly from adjustable collar (2562) and intovertical support arm (2520). As will be described in greater detailbelow, attachment shaft (2564) attaches adjustable collar (2562) tovertical support arm (2520) such that adjustable collar (2562) may beselectively rotated and translated relative to vertical support arm(2520).

The distal opening and proximal opening (2565) of adjustable collar(2562) define a lumen (not shown) extending through adjustable collar(2562). Openings (2565) are configured to receive slidable shaft (2568)such that slidable shaft (2568) may extend longitudinally throughadjustable collar (2562). As will be described in greater detail below,adjustable collar (2562) is configured to selectively lock and unlockslidable shaft (2568) such that slidable shaft (2568) may be selectivelytranslated within adjustable collar (2562) relative to vertical supportarm (2520).

Slidable shaft (2568) is generally ovular in shape and comprises acentral channel (2570) extending longitudinally through slidable shaft(2568). In some examples, central channel (2570) may receive pins orother features disposed within the lumen of adjustable collar (2562) tomaintain the horizontal position of slidable shaft (2568). Of course,such features are merely optional and may be omitted in some examples.

Attachment bracket (2572) is configured to receive at least a portion ofinstrument (2010) described above. In particular, attachment bracketcomprises (2572) an indexing pin (2574) and a quick release handle(2576). Indexing pin (2574) may engage a corresponding geometry ofinstrument (2010) to index the position of instrument (2010) relative toattachment bracket (2572). Quick release handle (2576) is incommunication with a mechanism within attachment bracket, which mayfacilitate the release of instrument (2010) from attachment bracket(2572) or attachment bracket (2572) from support assembly (2510). Itshould be understood that, in some examples, attachment bracket (2572)may include magnets that may engage corresponding magnets in instrument(2010) to permit quick attachment and detachment of instrument (2010)from support assembly (2510), in addition to or in lieu of includingquick release handle (2576).

An exemplary use of support assembly (2510) is shown in FIGS. 48 and 49.As can be seen, support assembly (2510) is movable through threeseparate ranges of motion (e.g., as indicated by arrows (2580, 2582,2584)). In particular, as can be seen in FIG. 48, support assembly(2510) may first be actuated vertically as indicated by arrow (2580). Topermit vertical actuation of support assembly (2510), an operator maypress button (2566), which actuates an internal mechanism insidevertical support arm (2520) thereby permitting adjustment through allthree ranges of motion. With attachment shaft (2564) free to rotate, anoperator may grasp lateral support arm (2560) and move lateral supportarm (2560) to a desired height.

Slidable shaft (2568) may also translate laterally relative to verticalsupport arm (2520) as indicated by arrow (2582). To translate slidableshaft (2568), an operator may press button (2566) to unlock translationof slidable shaft (2568). Although not shown, it should be understoodthat button (2566) may be in communication with a spring loaded lockingfeature or other similar apparatus that may be disengaged when button(2566) is pressed. While button (2566) is pressed, an operator may grasplateral support arm (2560) and move lateral support arm (2560) to adesired lateral position.

As can be seen in FIG. 49, lateral support arm (2560) may also berotated relative to vertical support arm (2520) as indicated by arrows(2584). Such rotation is initiated by also pressing button (2566) asdescribed above. In particular, pressing button (2566) actuates amechanism inside vertical support arm (2520) permiting rotation andtranslation of attachment shaft (2564) within vertical support arm(2520). With attachment shaft (2564) free to rotate, an operator maygrasp lateral support arm (2560) and rotate lateral support arm (2560)to a desired angular position. Other suitable ways in which supportassembly (2510) may be used will be apparent to those of ordinary skillin the art in view of the teachings herein. Similarly, other suitableways in which instrument (2010) may be supported will be apparent tothose of ordinary skill in the art in view of the teachings herein.

VI. Miscellaneous

Although the procedures and devices described herein are discussed inthe context of the treatment of age-related macular degeneration, itshould be understood that no such limitation is intended or implied. Theprocedures and devices described herein may be used to treat variousother kinds of medical conditions. By way of example only, theprocedures and devices described herein (and variations thereof) may beused to treat retinitis pigmentosa, diabetic retinopathy, wetage-related macular degeneration, and/or other medical conditions.Various suitable medical contexts in which the procedures and devicesdescribed herein may be used will be apparent to those of ordinary skillin the art.

It should be understood that any of the versions of the instrumentsdescribed herein may include various other features in addition to or inlieu of those described above. By way of example only, any of thedevices herein may also include one or more of the various featuresdisclosed in any of the various references that are incorporated byreference herein.

It should be understood that any one or more of the teachings,expressions, embodiments, examples, etc. described herein may becombined with any one or more of the other teachings, expressions,embodiments, examples, etc. that are described herein. Theabove-described teachings, expressions, embodiments, examples, etc.should therefore not be viewed in isolation relative to each other.Various suitable ways in which the teachings herein may be combined willbe readily apparent to those of ordinary skill in the art in view of theteachings herein. Such modifications and variations are intended to beincluded within the scope of the claims.

It should be appreciated that any patent, publication, or otherdisclosure material, in whole or in part, that is said to beincorporated by reference herein is incorporated herein only to theextent that the incorporated material does not conflict with existingdefinitions, statements, or other disclosure material set forth in thisdisclosure. As such, and to the extent necessary, the disclosure asexplicitly set forth herein supersedes any conflicting materialincorporated herein by reference. Any material, or portion thereof, thatis said to be incorporated by reference herein, but which conflicts withexisting definitions, statements, or other disclosure material set forthherein will only be incorporated to the extent that no conflict arisesbetween that incorporated material and the existing disclosure material.

Versions described above may be designed to be disposed of after asingle use, or they can be designed to be used multiple times. Versionsmay, in either or both cases, be reconditioned for reuse after at leastone use. Reconditioning may include any combination of the steps ofdisassembly of the device, followed by cleaning or replacement ofparticular pieces, and subsequent reassembly. In particular, someversions of the device may be disassembled, and any number of theparticular pieces or parts of the device may be selectively replaced orremoved in any combination. Upon cleaning and/or replacement ofparticular parts, some versions of the device may be reassembled forsubsequent use either at a reconditioning facility, or by an operatorimmediately prior to a procedure. Those skilled in the art willappreciate that reconditioning of a device may utilize a variety oftechniques for disassembly, cleaning/replacement, and reassembly. Use ofsuch techniques, and the resulting reconditioned device, are all withinthe scope of the present application.

By way of example only, versions described herein may be sterilizedbefore and/or after a procedure. In one sterilization technique, thedevice is placed in a closed and sealed container, such as a plastic orTYVEK bag. The container and device may then be placed in a field ofradiation that can penetrate the container, such as gamma radiation,x-rays, or high-energy electrons. The radiation may kill bacteria on thedevice and in the container. The sterilized device may then be stored inthe sterile container for later use. A device may also be sterilizedusing any other technique known in the art, including but not limited tobeta or gamma radiation, ethylene oxide, or steam.

Having shown and described various embodiments of the present invention,further adaptations of the methods and systems described herein may beaccomplished by appropriate modifications by one of ordinary skill inthe art without departing from the scope of the present invention.Several of such potential modifications have been mentioned, and otherswill be apparent to those skilled in the art. For instance, theexamples, embodiments, geometrics, materials, dimensions, ratios, steps,and the like discussed above are illustrative and are not required.Accordingly, the scope of the present invention should be considered interms of the following claims and is understood not to be limited to thedetails of structure and operation shown and described in thespecification and drawings.

I/We claim:
 1. An apparatus for delivering therapeutic agent to an eye,wherein the apparatus comprises: (a) a body; (b) a cannula extendingdistally from the body, wherein the cannula is sized and configured tobe insertable between a choroid and a sclera of a patient's eye, whereinthe cannula defines a longitudinal axis; (c) a hollow needle, whereinthe needle is slidable relative to the cannula; and (d) an actuationassembly, wherein the actuation assembly is operable to actuate theneedle relative to the cannula to thereby drive a distal portion of theneedle along an exit axis that is obliquely oriented relative to thelongitudinal axis of the cannula.
 2. The apparatus of claim 1, whereinthe actuation assembly includes an actuation member that is movablerelative to the body to actuate the needle.
 3. The apparatus of claim 2,wherein the actuation member is translatable relative to the body toactuate the needle.
 4. The apparatus of claim 2, wherein the actuationmember is rotatable relative to the body to actuate the needle.
 5. Theapparatus of claim 4, wherein the actuation assembly includes a threadedmember that is associated with the actuation member, wherein thethreaded member is configured to engage a threaded bore in the body toactuate the needle when the actuation member is rotated relative to thebody.
 6. The apparatus of claim 1, wherein the needle includes a sharpdistal tip.
 7. The apparatus of claim 6, wherein the sharp distal tip ofthe needle comprises a first bevel, a second bevel, and a third bevel,wherein the first bevel, second bevel, and third bevel are each orientedobliquely relative to each other.
 8. The apparatus of claim 1, whereinthe exit axis is oriented at an angle between approximately 5° andapproximately 30° relative to the longitudinal axis of the cannula. 9.The apparatus of claim 1, wherein the exit axis is oriented at an anglebetween approximately 7° and approximately 9° relative to thelongitudinal axis of the cannula
 10. The apparatus of claim 1, whereinthe cannula includes a blunt distal tip.
 11. The apparatus of claim 1,wherein the cannula includes a beveled distal end, wherein the beveleddistal end has a bevel angle, wherein the bevel angle is betweenapproximately 10° and approximately 30°.
 12. The apparatus of claim 1,wherein the cannula defines a plurality of lumens extendinglongitudinally through the length of the cannula, wherein at least onelumen of the plurality of lumens is configured to slidably receive theneedle.
 13. The apparatus of claim 1, wherein the cannula has a bendingstiffness between 0.7×10⁻⁶ Nm² and 11.1×10⁻⁶ Nm².
 14. The apparatus ofclaim 1, wherein the cannula has a bending stiffness between 2.0×10⁻⁶Nm² to 6.0×10⁻⁶ Nm².
 15. The apparatus of claim 1, further comprising avalve assembly, wherein the valve assembly is operable to provide afluid coupling between a fluid source and the needle, wherein the valveassembly is configured to translate with the needle relative to thebody.
 16. A method for use of a surgical instrument, wherein thesurgical instrument comprises a cannula and a hollow needle that ismovable relative to the cannula, the method comprising the steps of: (a)performing a sclerotomy by forming an incision in the eye of thepatient, wherein the incision extends through a sclera layer of the eyeto provide access to a suprachoroidal space of the eye; (b) insertingthe cannula through the sclerotomy; (c) advancing the cannula betweenthe choroid and the sclera to position the distal end of the cannula ata posterior region of the suprachoroidal space; (d) advancing the needlerelative to the cannula and through the choroid and into a subretialspace, without perforating the retina; and (e) delivering a therapeuticagent into the subretinal space via the advanced needle.
 17. The methodof claim 16, further comprising delivering a leading bleb of fluid viathe advanced needle before delivering the therapeutic agent via theadvanced needle.
 18. The method of claim 16, further comprisingattaching a suture loop to an eye of a patent, wherein the act ofattaching the suture loop includes threading a suture through the eye ofthe patient to form at least one loop defined by the suture, wherein theact of inserting the cannula comprises passing the cannula through thesuture loop.
 19. A method of suprachoroidially administering atherapeutic solution to an eye of a patient, the method comprising thesteps of: (a) threading a suture through the eye of the patient to format least one loop defined by the suture; (b) incising at least a portionof the eye to provide access to the choroid of the eye; (c) guiding acannula through the at least one loop defined by the suture and into anincision created by incising at least a portion of the eye; and (d)advancing a needle through the cannula to penetrate through the choroidand administer the therapeutic solution.
 20. The method of claim 19,wherein the method further comprises guiding the cannula to an injectionsite by direct visualization through the pupil of the eye of thepatient.